bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender-affirming Mastectomy: Comparison of Periareolar and Double Incision Patterns
Authors: Rifkin William J. , Robinson Isabel S. , Kloer Carmen , Cripps Courtney N. , Boyd Carter J. , Blasdel Gaines , Zhao Lee C. , Bluebond-Langner Rachel
Published: May 2022

Background:

Gender-affirming mastectomy has become one of the most frequently performed procedures for transgender and nonbinary patients. Although there are a variety of potential surgical approaches available, the impact of technique on outcomes remains unclear. Here we present our experience performing periareolar and double incision mastectomies, with a focus on comparing patient demographics, preoperative risk factors, and surgical outcomes and complication rates between techniques.

Methods:

Retrospective review identified patients undergoing gender-affirming mastectomy by the senior author between 2017 and 2020. Patients were stratified according to surgical technique, with demographics and postoperative outcomes compared between groups.

Results:

In total, 490 patients underwent gender-affirming mastectomy during the study period. An estimated 96 patients underwent periareolar mastectomy, whereas 390 underwent double incision mastectomy. Demographics were similar between groups, and there were no differences in rates of hematoma (3.1% versus 5.6%, respectively; P = 0.90), seroma (33.3% versus 36.4%; P = 0.52), or revision procedures (14.6% versus 15.8% P = 0.84) based on technique.

Conclusions:

Our results demonstrate no difference in the rates of postoperative complications or revision procedures based on surgical technique. These results also suggest that with an experienced surgeon and proper patient selection, both techniques of gender-affirming mastectomy can be performed safely and with comparable outcomes.
Bearing Extremes: Impacts from Simulated Outer Space Conditions and Effective Ultraviolet Radiation Shielding Materials on Tardigrade Life History
Authors: Zhu Amy , Stone Johnny
Published: May 2022

Questions about astrobiological resilience, whether entities with evolutionary histories on Earth would survive in outer space or on distant planets, for instance, no longer reside exclusively in the science fiction realm. In this study, we assess life history characteristics for individuals in the tardigrade species Grevenius annulatus post exposure to simulated outer space conditions with nonionizing radiation as a proxy for anticipated oxidative stress and damage incurred from exposure to full-spectrum environmental radiation. Using a planetary environment simulator, we exposed unshielded and shielded specimens to UVB and UVC radiation for 30 min and monitored and recorded subsequent life history characteristics. Survivorship was lower in an unshielded group relative to control as well as Kevlar and polyethylene shielded groups, demonstrating that Kevlar and polyethylene reduce impact from these types of nonionizing radiation, which are not expected to fully penetrate the shields. Cumulative egg production was lowest in the unshielded group, but egg viability and average egg production rate was highest. Due to insignificant differences, additional research to determine the relative effectiveness for Kevlar and polyethylene as shielding materials from survivorship and reproduction perspectives is warranted. This work provides a progressive step from which important conditions excluded in the current study, like vibrations, temperatures, debris-impacts, and ionizing radiation, can be included in future studies.
Ratios of Eye Lens and Hand Equivalent Doses with Whole-Body Effective Doses for Operators Performing Interventional Radiological Procedures
Authors: Tsai Wan-Chih , Chu Wei-Han , Sheu Rong-Jiun
Published: May 2022

Estimating radiation doses for operators performing interventional radiological procedures is crucial in the occupational radiation protection of medical staff. In this study, Monte Carlo simulations coupled with an anthropomorphic phantom were used to model various exposure scenarios during the procedures. Conversion coefficients of the dose-area product of x rays for the eye lens equivalent dose, hand equivalent dose, and whole-body effective dose of the operator were calculated. Accordingly, the relationships between these dose quantities in typical interventional configurations were established, considering various source locations, tube voltages, and use of protective equipment or not. The results are presented in a systematic way for easy comparison and use. Tables and figures of the data can be helpful to provide estimates of eye lens and hand equivalent doses when records of specific dosimeters are absent, such as in the retrospective assessment of operators’ eye lens and hand equivalent doses in past practices.
Postinjury complement C4 activation is associated with adverse outcomes and is potentially influenced by plasma resuscitation
Authors: Schaid Terry R. , Hansen Kirk C. , Sauaia Angela , Moore Ernest E. , DeBot Margot , Cralley Alexis L. , Erickson Christopher , Silliman Christopher C. , Banerjee Anirban , Ghasabyan Arsen , Jones Kenneth , Lacroix Ian , Mitra Sanchayita , D'Alessandro Angelo , Cohen Mitchell J.
Published: May 2022

BACKGROUND

Complement activation after trauma promotes hemostasis but is associated with increased morbidity and mortality. However, the specific pathways and downstream mediators remain unclear. Recently, the anaphylatoxin C4a has been shown to bind to thrombin receptors. While plasma-based resuscitation has been shown to modify the endotheliopathy of trauma, it may provide complement zymogens that fuel ongoing inflammatory cascades. We sought to characterize the activation of complement after injury and the effect of fresh frozen plasma (FFP) on this inflammatory response. We hypothesized that trauma induces C4 activation, which is associated with worse outcomes and influenced by FFP resuscitation.

METHODS

Blood was collected from injured patients at a single level I trauma center enrolled in the Control of Major Bleeding after Trauma (COMBAT) randomized clinical trial. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry. For the present observational study, concentrations of complement proteins were analyzed at multiple time points, compared between treatment groups, and correlated with outcomes.

RESULTS

C4 activation occurred over the first 6 hours postinjury with peak activation 6 to 24 hours. Tissue hypoperfusion, defined as base deficit >10 mEq/L, and requirement for massive transfusion were associated with greater C4 activation. C4 activation was associated with mortality, multiple organ failure, and longer ventilator requirement. In addition, temporal trends of C1q, factor B, and C3 by outcome groups support the prevailing theory of primary classical pathway activation with alternative pathway amplification. Resuscitation with FFP over the first 6 hours was associated with increased C4 activation at 12 and 24 hours.

CONCLUSION

C4 activation has an important inflammatory role postinjury, and FFP has the potential to augment this complement activation during resuscitation.

LEVEL OF EVIDENCE

Prognostic/epidemiological, level III.
Visual immersion: Daniele Barbaro's fish album and the wave of interest in aquatic creatures in mid sixteenth-century Europe
Authors: Egmond Florike
Published: May 2022

The mid sixteenth century wave of encyclopaedic publications about fish and other water creatures introduced massive numbers of newly made naturalia images. This article concentrates on the phase of image making and collecting that came
before
print. The focus is on the lost album with fish drawings created before 1551 by the Venetian humanist Daniele Barbaro and his personal painter Maestro Plinio. Naturalists such as Belon, Salviani and Aldrovandi borrowed and copied Barbaro's fish drawings. This case study indicates that a revolutionary visual turn took place before the 1550s in the domain of drawing, and was only in part connected with printing projects; that the notion of an encyclopaedic image collection of
aquatilia
was most likely inspired by innovations in botany; and that expert patron-collectors played a key role in it, setting visual trends and stimulating scientific passions.
Revisiting causality using stochastics: 1. Theory
Authors: Koutsoyiannis Demetris , Onof Christian , Christofides Antonis , Kundzewicz Zbigniew W.
Published: May 2022

Causality is a central concept in science, in philosophy and in life. However, reviewing various approaches to it over the entire knowledge tree, from philosophy to science and to scientific and technological applications, we locate several problems, which prevent these approaches from defining sufficient conditions for the existence of causal links. We thus choose to determine necessary conditions that are operationally useful in identifying or falsifying causality claims. Our proposed approach is based on stochastics, in which events are replaced by processes. Starting from the idea of stochastic causal systems, we extend it to the more general concept of hen-or-egg causality, which includes as special cases the classic causal, and the potentially causal and anti-causal systems. Theoretical considerations allow the development of an effective algorithm, applicable to large-scale open systems, which are neither controllable nor repeatable. The derivation and details of the algorithm are described in this paper, while in a companion paper we illustrate and showcase the proposed framework with a number of case studies, some of which are controlled synthetic examples and others real-world ones arising from interesting scientific problems.
Quantifying the impacts of 166 years of land cover change on lowland bird communities
Authors: Kitazawa Munehiro , Yamaura Yuichi , Senzaki Masayuki , Hanioka Masashi , Ohashi Haruka , Oguro Michio , Matsui Tetsuya , Nakamura Futoshi
Published: May 2022

Land cover change for agriculture is thought to be a major threat to global biodiversity. However, its ecological impact has rarely been quantified in the Northern Hemisphere, as broad-scale conversion to farmland mainly occurred until the 1400s–1700s in the region, limiting the availability of sufficient data. The Ishikari Lowland in Hokkaido, Japan, offers an excellent opportunity to address this issue, as hunter–gatherer lifestyles dominated this region until the mid-nineteenth century and land cover maps are available for the period of land cover changes (i.e. 1850–2016). Using these maps and a hierarchical community model of relationships between breeding bird abundance and land cover types, we estimated that broad-scale land cover change over a 166-year period was associated with more than 70% decline in both potential species richness and abundance of avian communities. We estimated that the abundance of wetland and forest species declined by greater than 88%, whereas that of bare-ground/farmland species increased by more than 50%. Our results suggest that broad-scale land cover change for agriculture has led to drastic reductions in wetland and forest species and promoted changes in community composition in large parts of the Northern Hemisphere. This study provides potential baseline information that could inform future conservation policies.
Blend in or stand out: social anxiety levels shape information-sharing strategies
Authors: Zaatri Silina , Aderka Idan M. , Hertz Uri
Published: May 2022

Although living in social groups provides many benefits for group members, such groups also serve as a setting for social competition over rank and influence. Evolutionary accounts suggest that social anxiety plays a role in regulating in-group conflict, as individuals who are concerned about social threat may choose to defer to others to maintain the hierarchical status quo. Here, we examine how social anxiety levels are related to the advice-giving style an individual adopts: a competitive influence-seeking strategy or a defensive blend-in strategy. We begin by demonstrating that similarity to others drives activity in the brain's valuation system, even during a competitive advice-taking task. Then, in three behavioural experiments, we show that social anxiety levels are related to the tendency to give advice resembling the advice given by rival advisers and to refrain from status-seeking behaviour. Social anxiety was also associated with negative social comparisons with rival advisers. Our findings highlight the role of competing social goals in shaping information sharing.
Evidence of attack deflection suggests adaptive evolution of wing tails in butterflies
Authors: Chotard Ariane , Ledamoisel Joséphine , Decamps Thierry , Herrel Anthony , Chaine Alexis S. , Llaurens Violaine , Debat Vincent
Published: May 2022

Predation is a powerful selective force shaping many behavioural and morphological traits in prey species. The deflection of predator attacks from vital parts of the prey usually involves the coordinated evolution of prey body shape and colour. Here, we test the deflection effect of hindwing (HW) tails in the swallowtail butterfly
Iphiclides podalirius
. In this species, HWs display long tails associated with a conspicuous colour pattern. By surveying the wings within a wild population of
I. podalirius
, we observed that wing damage was much more frequent on the tails. We then used a standardized behavioural assay employing dummy butterflies with real
I. podalirius
wings to study the location of attacks by great tits
Parus major
. Wing tails and conspicuous coloration of the HWs were struck more often than the rest of the body by birds. Finally, we characterized the mechanical properties of fresh wings and found that the tail vein was more fragile than the others, suggesting facilitated escape ability of butterflies attacked at this location. Our results clearly support the deflective effect of HW tails and suggest that predation is an important selective driver of the evolution of wing tails and colour pattern in butterflies.
Global ecomorphological restructuring of dominant marine reptiles prior to the Cretaceous–Palaeogene mass extinction
Authors: MacLaren Jamie A. , Bennion Rebecca F. , Bardet Nathalie , Fischer Valentin
Published: May 2022

Mosasaurid squamates were the dominant amniote predators in marine ecosystems during most of the Late Cretaceous. Here, we use a suite of biomechanically rooted, functionally descriptive ratios in a framework adapted from population ecology to investigate how the morphofunctional disparity of mosasaurids evolved prior to the Cretaceous–Palaeogene (K/Pg) mass extinction. Our results suggest that taxonomic turnover in mosasaurid community composition from Campanian to Maastrichtian is reflected by a notable global increase in morphofunctional disparity, especially driving the North American record. Ecomorphospace occupation becomes polarized during the late Maastrichtian, with morphofunctional disparity plateauing in the Southern Hemisphere and decreasing in the Northern Hemisphere. We show that these changes are not strongly associated with mosasaurid size, but rather with the functional capacities of their skulls. Our novel approach indicates that mosasaurid morphofunctional disparity was in decline in multiple provincial communities before the K/Pg mass extinction, highlighting region-specific patterns of disparity evolution and the importance of assessing vertebrate extinctions both globally and locally. Ecomorphological differentiation in mosasaurid communities, coupled with declines in other formerly abundant marine reptile groups, indicates widespread restructuring of higher trophic levels in marine food webs was well underway when the K/Pg mass extinction took place.
We get by with a little help from our friends: shared adaptive variation provides a bridge to novel ecological specialists during adaptive radiation
Authors: Richards Emilie J. , Martin Christopher H.
Published: May 2022

Adaptive radiations involve astounding bursts of phenotypic, ecological and species diversity. However, the microevolutionary processes that underlie the origins of these bursts are still poorly understood. We report the discovery of an intermediate
C.
sp. ‘wide-mouth’ scale-eating ecomorph in a sympatric radiation of
Cyprinodon
pupfishes, illuminating the transition from a widespread algae-eating generalist to a novel microendemic scale-eating specialist. We first show that this ecomorph occurs in sympatry with generalist
C. variegatus
and scale-eating specialist
C. desquamator
on San Salvador Island, Bahamas, but is genetically differentiated, morphologically distinct and often consumes scales. We then compared the timing of selective sweeps on shared and unique adaptive variants in trophic specialists to characterize their adaptive walk. Shared adaptive regions swept first in both the specialist
desquamator
and the intermediate ‘wide-mouth’ ecomorph, followed by unique sweeps of introgressed variation in ‘wide-mouth’ and de novo variation in
desquamator
. The two scale-eating populations additionally shared 9% of their hard selective sweeps with the molluscivore
C. brontotheroides
, despite no single common ancestor among specialists. Our work provides a new microevolutionary framework for investigating how major ecological transitions occur and illustrates how both shared and unique genetic variation can provide a bridge for multiple species to access novel ecological niches.
The pentatricopeptide repeat protein MTSF3 is required fornad2mRNA stability and embryogenesis in Arabidopsis
Authors: Wang Chuande , Blondel Lisa , Quadrado Martine , Dargel-Graffin Céline , Mireau Hakim
Published: May 2022

Gene expression in plant mitochondria is predominantly governed at the post-transcriptional level and relies mostly on nuclear-encoded proteins. However, the involved protein factors and the underlying molecular mechanisms are still not well understood. In this study, we report the function of the mitochondrial stability factor 3 (MTSF3) protein and we show that it is essential for accumulation of the mitochondrialnad2transcript in Arabidopsis and not for the splicing ofnad2intron 2, as recently proposed (Marchetti et al., 2020). The MTSF3 gene encodes a pentatricopeptide repeat protein that localizes in the mitochondrion. AnMTSF3null mutation induces embryonic lethality but viablemtsf3mutant plants could be generated by partial complementation with the developmentally-regulatedABSCISIC ACID INSENSITIVE3promoter. Genetic analyses reveal thatmtsf3rescued plants display growth retardation due to the specific destabilization of anad2precursor transcript bearing exons 3 to 5. Biochemical data demonstrate that MTSF3 protein specifically binds to the 3’-terminus ofnad2. The destabilization ofnad2mRNA induces a significant decrease in complex I assembly and activity, and an overexpression of the alternative respiratory pathway. Our results support that the MTSF3 protein protectsnad2transcript from degradation by mitochondrial exoribonucleases by binding to its 3’ extremity.
Analysis of the genetic diversity of SARS-CoV-2 genomes carrying the Omicron B.1.1.529 mutation
Authors: da Silva Bráulio Wagner Correia , Felix Pierre Teodosio
Published: May 2022

In this work, we evaluated the levels of genetic diversity in 95 genomes of the carriers of the Omicron B.1.1.529 mutation in SARS-CoV-2 from South Africa, Asia, Massachusetts-USA, Rhode Island-USA, United Kingdom and Germany. All with 29,996pb extension and recovered from GENBANK and publicly available at the National Center for Biotechnology and Information (NCBI). All gaps and conserved sites were extracted for the construction of a phylogenetic tree and for specific methodologies of estimates of paired FST, Molecular Variance (AMOVA), Genetic Distance, Incompatibility, demographic expansion analyses, molecular diversity and of evolutionary divergence time analyses, always with 20,000 random permutations. The results revealed the presence of only 75 parsimony-informative sites, sites among the 29,996bp analyzed. The analyses based on FSTvalues, confirmed the absence of distinct genetic structuring with fixation index of 98% and with a greater component of population variation (6%) for a “p” 0.05. Tau variations (related to the ancestry of the groups), did not reveal significant moments of divergence, supported by the incompatible analysis of the observed distribution (τ = 0%). It is safe to say that the large number of existing polymorphisms reflects major changes in the protein products of viral populations in all countries and especially In South Africa. This consideration provides the safety that, because there are large differences between the haplotypes studied, these differences are minimal within the populations analyzed geographically and, therefore, it does not seem safe to extrapolate the results of polymorphism and molecular diversity levels found in the Variant Omicron B.1.529 of SARS-CoV-2 for wild genomes or other mutants. This warns us that, due to their higher transmission speed and infection, possible problems of molecular adjustments in vaccines already in use may be necessary in the near future.
Associations between evening shift work, irregular sleep timing, and gestational diabetes in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b)
Authors: Wallace Danielle A , Reid Kathryn , Grobman William A , Facco Francesca L , Silver Robert M , Pien Grace W , Louis Judette , Zee Phyllis C , Redline Susan , Sofer Tamar
Published: May 2022

Study Objectives

Shift work is a risk factor for cardiometabolic disease, possibly through effects on sleep-wake rhythms. We hypothesized that shift work during pregnancy is associated with increased odds of preeclampsia, preterm birth, and gestational diabetes mellitus (GDM), and that the association is mediated by irregular sleep timing.

Methods

The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) is a prospective cohort study (n=10,038) designed to investigate risk factors for adverse pregnancy outcomes. Medical outcomes were determined with medical record abstraction and/or questionnaires; sleep midpoint was measured in a subset of participants with ≥5-day wrist actigraphy (ActiWatch). We estimated the association of shift work during pregnancy with preeclampsia, preterm birth, and GDM using logistic regression, adjusted for adversity (a cumulative variable for poverty, education, health insurance, and partner status), smoking, self-reported race/ethnicity, and age. Finally, we performed an analysis to explore the extent to which to the association between shiftwork and GDM was mediated by variability in sleep timing.

Results

Evening shift work during pregnancy is associated with approximately 75% increased odds of developing GDM (adjusted OR=1.75, 95% CI:1.12-2.66); there was no association with preterm birth and no association with preeclampsia after adjustment. Pregnant evening shift workers were found to have approximately 45 minutes greater variability in sleep timing compared to day workers (p<0.005); mediation analysis estimated that 27% of the association between shift work and GDM was explained by sleep-timing variability.

Conclusions

Evening shift work was associated with GDM, and this relationship may be mediated by variability in sleep timing.
Resolving heterogeneity in Diffuse Large B-cell Lymphoma using a comprehensive modular expression map
Authors: Care Matthew A. , Painter Daniel , Barrans Sharon , Sha Chulin , Johnson Peter , Davies Andy , Du Ming-Qing , Crouch Simon , Smith Alex , Roman Eve , Burton Cathy , Doody Gina , Westhead David , Klein Ulf , Hodson Daniel J. , Tooze Reuben
Published: May 2022

Diffuse large B-cell lymphoma (DLBCL) is characterised by pronounced genetic and biological heterogeneity. Several partially overlapping classification systems exist – developed from mutation, rearrangement or gene expression data. We apply a customised network analysis to nearly five thousand DLBCL cases to identify and quantify modules indicative of tumour biology. We demonstrate that network-level patterns of gene co-expression can enhance the separation of DLBCL cases. This allows the resolution of communities of related cases which correlate with genetic mutation and rearrangement status, supporting and extending existing concepts of disease biology and delivering insight into relationships between differentiation state, genetic subtypes, rearrangement status and response to therapeutic intervention. We demonstrate how the resulting fine-grained resolution of expression states is critical to accurately identify potential responses to treatment.

Significance statement

We demonstrate how exploiting data integration and network analysis of gene expression can enhance the segregation of diffuse large B-cell lymphoma, resolving pattens of disease biology and demonstrating how the resolution of heterogeneity can enhance the understanding of treatment response.
Diagnostic accuracy of the Panbio™ COVID-19 Antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation
Authors: Karuga Irungu , Munyua Peninah , Ochieng Caroline , Juma Bonventure , Amoth Patrick , Kuria Francis , Kiiru John , Makayotto Lyndah , Abade Ahmed , Bulterys Marc , Hunsperger Elizabeth , Emukule Gideon O. , Onyango Clayton , Samandari Taraz , Tippett Barr Beth A. , Akelo Victor , Weyenga Herman , Munywoki Patrick K , Bigogo Godfrey , Otieno Nancy A. , Kisivuli Jackton Azenga , Ochieng Edwin , Nyaga Rufus , Hull Noah , Herman-Roloff Amy , Aman Rashid
Published: May 2022

Background

Accurate and timely diagnosis is essential in limiting the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Real-time reverse transcription-polymerase chain reaction (rRT-PCR), the reference standard, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen rapid diagnostic tests (Ag RDTs) provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%.

Methods

This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention’s (CDC) rRT-PCR test.

Results

We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms >7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30.

Conclusion

The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool for only symptomatic patients in high-risk settings with limited access to RT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.
Measuring Community Resilience During the COVID-19 based on Community Wellbeing and Resource Distribution
Authors: Valinejad Jaber , Guo Zhen , Cho Jin-Hee , Chen Ing-Ray
Published: May 2022

The COVID-19 pandemic has severely harmed every aspect of our daily lives, resulting in a slew of social problems. Therefore, it is critical to accurately assess the current state of community functionality and resilience under this pandemic for successful recovery. To this end, various types of social sensing tools, such as tweeting and publicly released news, have been employed to understand individuals’ and communities’ thoughts, behaviors, and attitudes during the COVID-19 pandemic. However, some portions of the released news are fake and can easily mislead the community to respond improperly to disasters like COVID-19. This paper aims to assess the correlation between various news and tweets collected during the COVID-19 pandemic on community functionality and resilience. We use fact-checking organizations to classify news as real, mixed, or fake, and machine learning algorithms to classify tweets as real or fake to measure and compare community resilience (CR). Based on the news articles and tweets collected, we quantify CR based on two key factors, community wellbeing and resource distribution, where resource distribution is assessed by the level of economic resilience, and community capital. Based on the estimates of these two factors, we quantify CR from both news articles and tweets and analyze the extent to which CR measured from the news articles can reflect the actual state of CR measured from tweets. To improve the operationalization and sociological significance of this work, we use dimension reduction techniques to integrate the dimensions.
Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States
Authors: Flaxman Seth , Whittaker Charles , Semenova Elizaveta , Rashid Theo , Parks Robbie M , Blenkinsop Alexandra , Unwin H Juliette T , Mishra Swapnil , Bhatt Samir , Gurdasani Deepti , Ratmann Oliver
Published: May 2022

Covid-19 has caused more than 1 million deaths in the US, including at least 1,204 deaths among children and young people (CYP) aged 0-19 years, with 796 occurring in the one year period April 1, 2021 - March 31, 2022. Deaths among US CYP are rare in general, and so we argue here that the mortality burden of Covid-19 in CYP is best understood in the context of all other causes of CYP death. Using publicly available data from CDC WONDER on NCHS’s 113 Selected Causes of Death, and comparing to mortality in 2019, the immediate pre-pandemic period, we find that Covid-19 mortality is among the 10 leading causes of death in CYP aged 0-19 years in the US, ranking 8th among all causes of deaths, 5th in disease-related causes of deaths (excluding accidents, assault and suicide), and 1st in deaths caused by infectious or respiratory diseases. Covid-19 deaths constitute 2.3% of the 10 leading causes of death in this age group. Covid-19 caused substantially more deaths in CYP than major vaccine-preventable diseases did historically in the period before vaccines became available. Various factors including underreporting and Covid-19’s role as a contributing cause of death from other diseases mean that our estimates may understate the true mortality burden of Covid-19. Our findings underscore the public health relevance of Covid-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, pharmaceutical and non-pharmaceutical interventions will continue to play an important role in limiting transmission of the virus in CYP and mitigating severe disease.
Humoral Immunity to SARS-CoV-2 and Inferred Protection from Infection in a French Longitudinal Community Cohort
Authors: Woudenberg Tom , Pinaud Laurie , Garcia Laura , Tondeur Laura , Pelleau Stéphane , De Thoisy Alix , Donnadieu Françoise , Backovic Marija , Attia Mikaël , Hozé Nathanael , Duru Cécile , Koffi Aymar Davy , Castelain Sandrine , Ungeheuer Marie-Noelle , Pellerin Sandrine Fernandes , Planas Delphine , Bruel Timothée , Cauchemez Simon , Schwartz Olivier , Fontanet Arnaud , White Michael
Published: May 2022

Population-level immunity to SARS-CoV-2 is growing through vaccination as well as ongoing circulation. Given waning immunity and emergence of new variants, it is important to dynamically determine the risk of re-infection in the population. For estimating immune protection, neutralization titers are most informative, but these assays are difficult to conduct at a population level. Measurement of antibody levels can be implemented at high throughput, but has not been robustly validated as a correlate of protection. Here, we have developed a method that predicts neutralization and protection based on variant-specific antibody measurements to SARS-CoV-2 antigens. This approach allowed us to estimate population-immunity in a longitudinal cohort from France followed for up to 2 years. Participants with a single vaccination or immunity caused by infection only are especially vulnerable to COVID-19 or hospitalization due to SARS-CoV-2. While the median reduced risk to COVID-19 in participants with 3 vaccinations was 96%, the median reduced risk among participants with infection-acquired immunity only was 42%. The results presented here are consistent with data from vaccine-effectiveness studies indicating robustness of our approach. Our multiplex serological assay can be readily optimized and employed to study any new variant and provides a framework for development of an assay that would include protection estimates.
Sex differences in the nasal microbiome of healthy young adults
Authors: Ju Yanmei , Zhang Zhe , Liu Mingliang , Lin Shutian , Sun Qiang , Song Zewei , Liang Weiting , Tong Xin , Jie Zhuye , Lu Haorong , Cai Kaiye , Chen Peishan , Jin Xin , Xu Xun , Yang Huanming , Wang Jian , Hou Yong , Xiao Liang , Jia Huijue , Zhang Tao , Guo Ruijin
Published: May 2022

Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections (RTIs) between males and females. It is recently hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities, but without evidence. In this work, we study the nasal microbiome of healthy young adults in, as of today, the largest cohort based on deep shot-gun metagenomic sequencing. We mainly focus on the bacteriome, but also integrate the mycobiome to get a more holistic perspective. De novo assembly is performed to catalog the nasal bacterial colonizers/residents, which also identify and therefore account for uncharacterized components of the community. The bacteriome is then profiled based on the non-redundant metagenome-assembled genomes (MAGs) catalog constructed therefrom. Unsupervised clustering reveals clearly separable structural patterns in the nasal microbiome between the two sexes. Following this link, we systematically evaluate sex differences for the first time and reveal extensive sex-specific features in the nasal microbiome composition. More importantly, through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the nasal microbiome of females than that of males. The analysis of the keystone bacteria of the communities reveal that the sex-dependent evolutionary characteristics might have contributed to this difference.

Highlights

The non-redundant nasal bacterial MAGs catalog constructed from ultra-deeply sequenced metagenomic data provides a valuable resource.

Integrating nasal bacteriome and mycobiome data provides a more holistic perspective for the understudied human nasal microbiome.

Unsupervised clustering helps uncover extensive sex differences in the nasal microbiome compositions.

Network analyses capture markedly higher ecological stability and antagonistic potentials in the nasal microbiome of females than that of males.

Sex-dependent genetic evolutionary forces play a role in the shaping of keystones in the nasal microbial community.
High-throughput deep learning variant effect prediction with Sequence UNET
Authors: Dunham Alistair S. , Beltrao Pedro , AlQuraishi Mohammed
Published: May 2022

Understanding the consequences of protein coding mutations is important for many applications in biology and medicine. The vast number of possible mutations across species makes comprehensive experimental characterisation impossible, even with recent high-throughput techniques, which means computationally predicting the consequences of variation is essential for many analyses. Previous variant effect prediction (VEP) tools, generally based on evolutionary conservation and protein structure, are often computationally intensive, making them difficult to scale and limiting potential applications. Recent developments in deep learning techniques, including protein language models, and biological data scale have led to a new generation of predictors. These models have improved prediction performance but are still often intensive to run because of slow training steps, hardware requirements and large model sizes. In this work we introduce a new highly scalable deep learning architecture, Sequence UNET, that classifies and predicts variant frequency directly from protein sequence. This model learns to build representations of protein sequence features at a range of scales using a fully convolutional U-shaped compression/expansion architecture. We show that it can generalise to pathogenicity prediction, achieving comparable performance on ClinVar to methods including EVE and ESM-1b at greatly reduced computational cost. We further demonstrate its scalability by analysing the consequences of 8.3 billion variants in 904,134 proteins detected in a large-scale proteomics analysis, showing a link between conservation and protein abundance. Sequence UNET can be run on modest hardware through an easy to use Python package.
Accurate angular integration with only a handful of neurons
Authors: Noorman Marcella , Hulse Brad K , Jayaraman Vivek , Romani Sandro , Hermundstad Ann M
Published: May 2022

To flexibly navigate, many animals rely on internal spatial representations that persist when the animal is standing still in darkness, and update accurately by integrating the animal’s movements in the absence of localizing sensory cues. Theories of mammalian head direction cells have proposed that these dynamics can be realized in a special class of networks that maintain a localized bump of activity via structured recurrent connectivity, and that shift this bump of activity via angular velocity input. Although there are many different variants of these so-called ring attractor networks, they all rely on large numbers of neurons to generate representations that persist in the absence of input and accurately integrate angular velocity input. Surprisingly, in the fly, Drosophila melanogaster, a head direction representation is maintained by a much smaller number of neurons whose dynamics and connectivity resemble those of a ring attractor network. These findings challenge our understanding of ring attractors and their putative implementation in neural circuits. Here, we analyzed failures of angular velocity integration that emerge in small attractor networks with only a few computational units. Motivated by the peak performance of the fly head direction system in darkness, we mathematically derived conditions under which small networks, even with as few as 4 neurons, achieve the performance of much larger networks. The resulting description reveals that by appropriately tuning the network connectivity, the network can maintain persistent representations over the continuum of head directions, and it can accurately integrate angular velocity inputs. We then analytically determined how performance degrades as the connectivity deviates from this optimally-tuned setting, and we find a trade-off between network size and the tuning precision needed to achieve persistence and accurate integration. This work shows how even small networks can accurately track an animal’s movements to guide navigation, and it informs our understanding of the functional capabilities of discrete systems more broadly.
Development of an In Vitro Test for the Optimization of Drug Diffusion in Pediatric Solid Tumors
Authors: Ivy Rachel , Hendricks-Wenger Alissa , Kennedy Lyndon , Jones Anna , Riley Deanna , Handy Ashley , Barker Elizabeth D.
Published: May 2022

There is significant long-term morbidity and mortality associated with the treatment of childhood cancer, and the risk of these effects continues to increase years after completion of therapy. Among childhood cancer survivors the cumulative incidence of a chronic health condition is 99% within 50 years of the original cancer diagnosis. There is a high risk for severe, disabling, or life-threatening chronic condition caused by the chemotherapy used to treat the initial malignancy. Current standards for determining chemotherapy dosage to treat solid tumor malignancies of pediatric patients is based on several factors, including the patient’s surface area, age, weight, and height. To reduce the long-term effects of chemotherapy in pediatric patients our group is focused on developing novel local drug delivery systems to treat solid tumors and minimize systemic effects. The aim of the current study is to develop anin vitromethod to quantify drug diffusion through tumor tissue that will allow us to optimize the dose required to treat solid tumor malignanciesin vivo. We hope by modeling the significant parameters that influence drug penetration of chemotherapy drugs, we can facilitate the development of innovative drug delivery methods and more effective administration of anticancer agents to better treat pediatric malignancies and improve both short-term and long-term outcomes for childhood cancer.
A partially averaged system to model neuron responses to interferential current stimulation
Authors: Cerpa Eduardo , Courdurier Matías , Hernández Esteban , Medina Leonel E. , Paduro Esteban
Published: May 2022

The interferential current (IFC) therapy is a noninvasive electrical neurostimulation technique intended to activate deep neurons using surface electrodes. In IFC, two independent kilohertz-frequency currents purportedly intersect where an interference field is generated. However, the effects of IFC on neurons within and outside the interference field are not completely understood, and it is unclear whether this technique can reliable activate deep target neurons without side effects. In recent years, realistic computational models of IFC have been introduced to quantify the effects of IFC on brain cells, but they are often complex and computationally costly. Here, we introduce a simplified model of IFC based on the FitzHugh-Nagumo (FHN) model of a neuron. By considering a modified averaging method, we obtain a non-autonomous approximated system, with explicit representation of relevant IFC parameters. For this approximated system we determine conditions under which it reliably approximates the complete FHN system under IFC stimulation, and we mathematically prove its ability to predict nonspiking states. In addition, we perform numerical simulations that show that the interference effect is observed only for a narrow set of IFC parameters and, in particular, for a beat frequency no higher than about 100 [Hz]. Our novel model tailored to the IFC technique contributes to the understanding of neurostimulation modalities using this type of signals, and can have implications in the design of noninvasive electrical stimulation therapies.
An Engineered Amber-Emitting Nano Luciferase and Its Use for Immunobioluminescence Imaging in Vivo
Authors: Xiong Ying , Zhang Yiyu , Li Zefan , Reza Md Shamim , Li Xinyu , Tian Xiaodong , Ai Huiwang
Published: May 2022

The NanoLuc luciferase (NLuc) and its furimazine (FRZ) substrate have revolutionized bioluminescence (BL) assays and imaging. However, the use of the NLuc-FRZ luciferase-luciferin pair for mammalian tissue imaging is hindered by the low tissue penetration of the emitting blue photons. Here, we present the development of an NLuc mutant, QLuc, which catalyzes the oxidation of a synthetic QTZ luciferin for bright and red-shifted emission peaking at ∼ 585 nm. This amber-light-emitting luciferase-luciferin pair exhibited improved performance for imaging deep-tissue targets in live mice. Leveraging this novel bioluminescent reporter, we further pursued in vivo immunobioluminescence imaging (immunoBLI), which used a fusion protein of a single-chain variable antibody fragment (scFv) and QLuc for molecular imaging of tumor-associated antigens in a xenograft mouse model. As one of the most red-shifted NLuc variants, we expect QLuc to find broad applications in noninvasive imaging in mammals. Moreover, the immunoBLI method complements immunofluorescence imaging and immuno-positron emission tomography (immunoPET), serving as a convenient and nonradioactive molecular imaging tool for animal models in basic and preclinical research.
A Wars2 mutant mouse shows a sex and diet specific change in fat distribution, reduced food intake and depot-specific upregulation of WAT browning
Authors: Mušo Milan , Bentley Liz , Vizor Lucie , Yon Marianne , Burling Keith , Barker Peter , Zolkiewski Louisa A K , Cox Roger D , Dumbell Rebecca
Published: May 2022

1.

Background

Increased waist-to-hip ratio (WHR) is associated with increased mortality and risk of type 2 diabetes and cardiovascular disease. The TBX15-WARS2 locus has consistently been associated with increased WHR. Previous study of the hypomorphic Wars2V117L/V117L mouse model found phenotypes including severely reduced fat mass, and white adipose tissue (WAT) browning, suggesting Wars2 could be a potential modulator of fat distribution and WAT browning.

Methods

To test for differences in browning induction across different adipose depots of Wars2V117L/V117L mice, we measured multiple browning markers of a 4-month old chow-fed cohort in subcutaneous and visceral WAT and brown adipose tissue (BAT). To explain previously observed fat mass loss, we also tested for the upregulation of plasma mitokines FGF21 and GDF15 and for differences in food intake in the same cohort. Finally, to test for diet-associated differences in fat distribution, we placed Wars2V117L/V117L mice on low-fat or high-fat diet (LFD, HFD) and assessed their body composition by Echo-MRI and compared terminal adipose depot weights at 6 months of age.

Results

The chow-fed Wars2V117L/V117L mice showed more changes in WAT browning marker gene expression in the subcutaneous inguinal WAT depot (iWAT) than in the visceral gonadal WAT depot (gWAT). These mice also demonstrated reduced food intake and elevated plasma FGF21 and GDF15, and mRNA from heart and BAT. When exposed to HFD, the Wars2V117L/V117L mice showed resistance to diet-induced obesity and a male and HFD-specific reduction of gWAT : iWAT ratio.

Conclusion

Severe reduction of Wars2 gene function causes a systemic phenotype which leads to upregulation of FGF21 and GDF15, resulting in reduced food intake and depot-specific changes in browning and fat mass.
Design of Peptide-Based Protein Degraders via Contrastive Deep Learning
Authors: Palepu Kalyan , Ponnapati Manvitha , Bhat Suhaas , Tysinger Emma , Stan Teodora , Brixi Garyk , Koseki Sabrina R.T. , Chatterjee Pranam
Published: May 2022

Abstract

Therapeutic modalities targeting pathogenic proteins are the gold standard of treatment for multiple disease indications. Unfortunately, a significant portion of these proteins are considered “undruggable” by standard small molecule-based approaches, largely due to their disordered nature and instability. Designing functional peptides to undruggable targets, either as standalone binders or fusions to effector domains, thus presents a unique opportunity for therapeutic intervention. In this work, we adapt recent models for contrastive language-image pre-training (CLIP) to devise a unified, sequence-based framework to design target-specific peptides. Furthermore, by leveraging known experimental binding proteins as scaffolds, we create a streamlined inference pipeline, termed Cut&CLIP, that efficiently selects peptides for downstream screening. Finally, we experimentally fuse candidate peptides to E3 ubiquitin ligase domains and demonstrate robust intracellular degradation of pathogenic protein targets in human cells, motivating further development of our technology for future clinical translation.