bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental influences on breeding biology and pup production in Australian fur seals
Authors: Geeson Johanna J. , Hobday Alistair J. , Speakman Cassie N. , Arnould John P. Y.
Published: April 2022

Knowledge of factors affecting a species' breeding biology is crucial to understanding how environmental variability impacts population trajectories and enables predictions on how species may respond to global change. The Australian fur seal (Arctocephalus pusillus doriferus, AUFS) represents the largest marine predator biomass in southeastern Australia, an oceanic region experiencing rapid warming that will impact the abundance and distribution of prey. The present study (1997–2020) investigated breeding phenology and pup production in AUFS on Kanowna Island, northern Bass Strait. The pupping period varied by 11 days and the median pupping date by 8 days and were negatively correlated to 1- and 2-year lagged winter zonal winds, respectively, within Bass Strait. While there was no temporal trend over the study period, annual pup production (1386–2574 pups) was negatively correlated to 1-year lagged summer zonal winds in the Bonney Upwelling region and positively correlated to the current-year Southern Oscillation Index (SOI). In addition, a fecundity index (ratio of new-born pups to adult females at the median pupping date) was positively correlated with current-year Southern Annular Mode (SAM) conditions. Periods of positive SOI and positive SAM conditions are forecast to increase in coming decades, suggesting advantageous conditions for the Kanowna Island AUFS population.
Interference of internal waves due to two point vortices: linear analytical solution and nonlinear interaction
Authors: Wang Zhen , Liu Di , An Xiaoqin
Published: April 2022

In this work, we consider steady two-dimensional interfacial waves in a two-layer stratified fluid, which is induced by a vortex pair located in the lower layer of the fluids. A mathematical model based on the boundary integral equation method and the potential-flow theory is established. The linear analytical solution for the linearized model is given in the form of Cauchy integral and then asymptotic behaviour for large x is presented. The fully nonlinear model is solved by the Jacobian-free Newton–Krylov (JFNK) method numerically. Nonlinear characteristics of wave profiles are identified compared with the linear results under different vortex strengths and the distance between the vortex pair. The amplitude of steady downstream waves is found to vary periodically with respect to the distance of the vortex pair, which can be regarded as the interference between waves produced by each vortex. For equal-strength counter- and co-rotating pairs, the downstream wave heights of linear solutions can be eliminated for some special values of the distance between point vortices, namely, the destructive interference occurs. Meanwhile, the wave only exists between the vortex pair like trapped waves. So does the nonlinear counterpart for counter-rotating pairs, but it could not be diminished with any distance.
Transverse spectral instability in generalized Kadomtsev–Petviashvili equation
Authors: Bhavna  , Kumar Atul , Pandey Ashish Kumar
Published: April 2022

We study transverse stability and instability of one-dimensional small-amplitude periodic travelling waves of a generalized Kadomtsev–Petviashvili equation with respect to two-dimensional perturbations, which are either periodic or square-integrable in the direction of the propagation of the underlying one-dimensional wave and periodic in the transverse direction. We obtain transverse instability results in KP-fKdV, KP-ILW and KP-Whitham equations. Moreover, assuming the spectral stability of one-dimensional wave with respect to one-dimensional square-integrable periodic perturbations, we obtain transverse stability results in the aforementioned equations.
Rigid folding equations of degree-6 origami vertices
Authors: Farnham Johnna , Hull Thomas C. , Rumbolt Aubrey
Published: April 2022

Rigid origami, with applications ranging from nano-robots to unfolding solar sails in space, describes when a material is folded along straight crease line segments while keeping the regions between the creases planar. Prior work has found explicit equations for the folding angles of a flat-foldable degree-4 origami vertex and some cases of degree-6 vertices. We extend this work to generalized symmetries of the degree-6 vertex where all sector angles equal

60
∘

. We enumerate the different viable rigid folding modes of these degree-6 crease patterns and then use second-order Taylor expansions and prior rigid folding techniques to find algebraic folding angle relationships between the creases. This allows us to explicitly compute the configuration space of these degree-6 vertices, and in the process we uncover new explanations for the effectiveness of Weierstrass substitutions in modelling rigid origami. These results expand the toolbox of rigid origami mechanisms that engineers and materials scientists may use in origami-inspired designs.
A novel statistical framework for exploring the population dynamics and seasonality of mosquito populations
Authors: Whittaker Charles , Winskill Peter , Sinka Marianne , Pironon Samuel , Massey Claire , Weiss Daniel J. , Nguyen Michele , Gething Peter W. , Kumar Ashwani , Ghani Azra , Bhatt Samir
Published: April 2022

Understanding the temporal dynamics of mosquito populations underlying vector-borne disease transmission is key to optimizing control strategies. Many questions remain surrounding the drivers of these dynamics and how they vary between species—questions rarely answerable from individual entomological studies (that typically focus on a single location or species). We develop a novel statistical framework enabling identification and classification of time series with similar temporal properties, and use this framework to systematically explore variation in population dynamics and seasonality in anopheline mosquito time series catch data spanning seven species, 40 years and 117 locations across mainland India. Our analyses reveal pronounced variation in dynamics across locations and between species in the extent of seasonality and timing of seasonal peaks. However, we show that these diverse dynamics can be clustered into four ‘dynamical archetypes’, each characterized by distinct temporal properties and associated with a largely unique set of environmental factors. Our results highlight that a range of environmental factors including rainfall, temperature, proximity to static water bodies and patterns of land use (particularly urbanicity) shape the dynamics and seasonality of mosquito populations, and provide a generically applicable framework to better identify and understand patterns of seasonal variation in vectors relevant to public health.
Erwinia phyllosphaerae sp. nov., a novel bacterium isolated from phyllosphere of pomelo (Citrus maxima)
Authors: Pan Ming-Kai , Feng Guang-Da , Yao Qing , Li Jiali , Liu Chenjian , Zhu Honghui
Published: April 2022

A novel phosphate-solubilizing and 3-indoleacetic acid producing bacterium, designated strain CMYE1T, was isolated from the phyllosphere of pomelo (Citrus maxima) in Meizhou, Guangdong Province, PR China. Cells were Gram-stain-negative, facultative aerobic, non-spore-forming, rod-shaped and motile with peritrichous flagella. It had the highest 16S rRNA gene sequence similarity to

Kalamiella piersonii

NRRL B-65522T (99.0 %), followed by

Pantoea cypripedii

LMG 2657T (98.1 %),

Erwinia iniecta

B120T (97.7 %),

Mixta intestinalis

29Y89BT (97.6 %) and other species (<97.6 %). However, phylogenomic analyses clearly showed that strain CMYE1T should be assigned into the genus

Erwinia

, and was most closely related to

Erwinia oleae

LMG 25322T (96.7 %). Genome comparisons showed that the novel strain shared ≤83.2 % average nucleotide identity and ≤26.5 % digital DNA–DNA hybridization values with closely related strains, respectively. It contained C16 : 0, C17 : 0 cyclo, summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c) and summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c) as the major fatty acids. Based on the results of phylogenetic, phenotypic and chemotaxonomic analyses, as well as genome comparisons, strain CMYE1T belongs to a novel species of the genus

Erwinia

, for which the name Erwinia phyllosphaerae sp. nov. is proposed with the type strain CMYE1T (=GDMCC 1.2674T=JCM 34792T).
Effect of RNA quality to SARS-CoV-2 RT-qPCR detection from saliva
Authors: Paju Susanna , Tallgren Marika , Kivimäki Anne , Lahdentausta Laura , Salminen Aino , Oksanen Lotta , Sanmark Enni , Geneid Ahmed , Pussinen Pirkko , Pietiäinen Milla
Published: April 2022

Saliva is an alternative sample material to nasopharyngeal swab in SARS-CoV-2 diagnostics. We investigated possible aspects to improve the reliability of SARS-CoV-2 detection from saliva. Saliva was collected from asymptomatic healthy subjects (n=133) and COVID-19 patients (n=9). SARS-CoV-2 detection was performed with quantitative reverse-transcriptase PCR (RT-qPCR) with two viral and one host target serving as an internal control. The use of internal control revealed that in the first RT-qPCR run 25–30 % of assays failed. The failure is associated with poor RNA quality. When the amount of RNA was cut down to half from the original amount, the performance of RT-qPCR was greatly enhanced (95 % of the assays succeeded). The quality of RNA was not affected by the use of different nucleic acid stabilizing buffers. Our study showed that saliva is suitable material for RT-qPCR based SARS-CoV-2 diagnostics, but the use of internal control is essential to distinguish the true negative samples from failed assays.
Linear plasmids in Klebsiella and other Enterobacteriaceae
Authors: Hawkey Jane , Cottingham Hugh , Tokolyi Alex , Wick Ryan R. , Judd Louise M. , Cerdeira Louise , de Oliveira Garcia Doroti , Wyres Kelly L. , Holt Kathryn E.
Published: April 2022

Linear plasmids are extrachromosomal DNA elements that have been found in a small number of bacterial species. To date, the only linear plasmids described in the family

Enterobacteriaceae

belong to

Salmonella

, first found in

Salmonella enterica

Typhi. Here, we describe a collection of 12 isolates of the

Klebsiella pneumoniae

species complex in which we identified linear plasmids. Screening of assembly graphs assembled from public read sets identified linear plasmid structures in a further 13

K

.

pneumoniae

species complex genomes. We used these 25 linear plasmid sequences to query all bacterial genome assemblies in the National Center for Biotechnology Information database, and discovered an additional 61 linear plasmid sequences in a variety of

Enterobacteriaceae

species. Gene content analysis divided these plasmids into five distinct phylogroups, with very few genes shared across more than two phylogroups. The majority of linear plasmid-encoded genes are of unknown function; however, each phylogroup carried its own unique toxin–antitoxin system and genes with homology to those encoding the ParAB plasmid stability system. Passage in vitro of the 12 linear plasmid-carrying

Klebsiella

isolates in our collection (which include representatives of all five phylogroups) indicated that these linear plasmids can be stably maintained, and our data suggest they can transmit between

K. pneumoniae

strains (including members of globally disseminated multidrug-resistant clones) and also between diverse

Enterobacteriaceae

species. The linear plasmid sequences, and representative isolates harbouring them, are made available as a resource to facilitate future studies on the evolution and function of these novel plasmids.
“It is guiding us to protect ourselves”: a qualitative investigation into why young people engage with a mass-media HIV education campaign
Authors: Baker Venetia , Mulwa Sarah , Sarrassat Sophie , Khanyile David , Cawood Cherie , Cousens Simon , Birdthistle Isolde
Published: April 2022

This study explores how and why young people engage with MTV Shuga, a popular mass media edutainment campaign, to understand what makes effective HIV education. Young MTV Shuga viewers from the Eastern Cape, South Africa and their parents participated in remote individual interviews and focus groups in 2020. Qualitative data were transcribed and analysed using a thematic iterative approach. Young participants engaged with MTV Shuga for relatable, tolerant, and complex stories about young people navigating HIV and relationships. These stories, which made viewers aware of sexual health services, inspired young people to reflect on how they would approach sexual health scenarios. MTV Shuga initiated conversations among peers, partners and some families about HIV that made them feel supported and equipped to tackle problems in their own lives. Storytelling can make HIV education engaging and relatable as it guides young people through sexual health situations. Storytelling can empower young people to make their own informed decisions while allowing space for uncertainty and diverse opinions about HIV and sexual health. Media-based storytelling can disseminate knowledge into homes and start conversations about HIV in the broader community. Increasing digitally-unconnected youths’ access to media-based interventions is essential to making HIV education more equitable.
SIGNIFICANT IMPROVEMENT IN MELANOMA SURVIVAL OVER THE LAST DECADE: A HUNGARIAN NATIONWIDE STUDY BETWEEN 2011–2019
Authors: Liszkay Gabriella , Benedek Angela , Polgár Csaba , Oláh Judit , Holló Péter , Emri Gabriella , Csejtei András , Kenessey István , Polányi Zoltán , Knollmajer Kata , Várnai Máté , Vokó Zoltán , Nagy Balázs , Rokszin György , Fábián Ibolya , Barcza Zsófia , Gyulai Rolland , Kiss Zoltan
Published: April 2022

Background

Recent real-world studies have reported significant improvements in the survival of malignant melanoma in the past few years, mainly as a result of modern therapies. However, long-term survival data from Central Eastern European countries such as Hungary are currently lacking.

Methods

This nationwide, retrospective study examined melanoma survival in Hungary between 2011–2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Crude overall survival and age-standardized 5-year net survival as well as the association between age, sex, and survival were calculated.

Results

Between 2011 and 2019, 22,948 newly diagnosed malignant melanoma cases were recorded in the NHIF database (47.89% male, mean age: 60.75 years (SD: ±16.39)). 5-year overall survival was 75.40% (women: 80.78%; men: 69.52%). Patients diagnosed between 2017–2019 had a 20% lower risk of mortality compared to patients diagnosed between 2011–2012 (HR 0.80, 95% CI 0.73–0.89; p<0.0001). Age-standardized 5-year net survival rates in 2011–2014 and 2015–2019 were 90.6% and 95.8%, respectively (women: 93.1% and 98.4%, men: 87.8% and 92.7%, respectively). The highest age-standardized 5-year net survival rates were found in the 0–39 age cohort (94.6% in the 2015-2019 period).

Conclusion

Hungary has similar melanoma survival rates to Western European countries. Based on net survival, the risk of dying of melanoma within 5 years was cut by more than half (55%) during the study period, which coincides with the successful implementation of awareness campaigns and the wide availability of modern therapies.
Determinants of facility-based childbirth among adolescents and young women in Guinea: a secondary analysis of the 2018 Demographic and Health Survey
Authors: Grovogui Fassou Mathias , Benova Lenka , Manet Hawa , Sidibe Sidikiba , Dioubate Nafissatou , Camara Bienvenu Salim , Beavogui Abdoul Habib , Delamou Alexandre
Published: April 2022

Introduction

Maternal mortality remains very high in Sub-Saharan African countries and the risk is higher among adolescent girls. Maternal mortality occurs in these settings mainly around the time of childbirth and the first 24 hours after birth. Therefore, skilled attendance in an enabling environment is essential to reduce the occurrence of adverse outcomes for both women and their children. This study aims to analyze the determinants of facility childbirth among adolescents and young women in Guinea.

Methods

We used the Guinea Demographic and Health Survey (DHS) conducted in 2018. All females who were adolescents (15 -19) or young women (20-24 years) at the time of their most recent live birth in the five years before the survey were included. We examined the use of health facilities for childbirth and its determinants using multivariable logistic regression, built through the Andersen health-seeking model.

Results

Overall, 58% of adolescents and 57% of young women gave birth in a health facility. Young women were more likely to have used private sector facilities compared to adolescents (p<0.001). Factors significantly associated with a facility birth in multivariable regression included: secondary or higher educational level (aOR=1.81; 95%CI:1.20-2.64) compared to no formal education; receipt of 1-3 antenatal visits (aOR=8.93; 95%CI: 5.10-15.55) and 4+ visits (aOR=15.1; 95%CI: 8.50-26.84) compared to none; living in urban (aOR=2.13; 95%CI: 1.40-3.37) compared to rural areas. Women from poorest households were least likely to give birth in health facilities. There was substantial variation in the likelihood of birth in a health facility by region, with highest odds in NZérékoré and lowest in Labé.

Conclusion

The percentage of births in health facilities among adolescents and young women in Guinea increased since 2012 but remains suboptimal. Socio-economic characteristics, region of residence and antenatal care use were the main determinants of its use. Efforts to improve maternal health among this group should target care discontinuation between antenatal care and childbirth (primarily by removing financial barriers) and increasing the demand for facility-based childbirth services in communities, while paying attention to the quality and respectful nature of healthcare services provided there.
COVID-19 vaccine for people who live and work in prisons worldwide: A scoping review
Authors: Ismail Nasrul , Tavoschi Lara , Moazen Babak , Roselló Alicia , Plugge Emma
Published: April 2022

Overcrowding, poor conditions, and high population turnover make prisons highly susceptible to COVID-19. Vaccination is key to controlling COVID-19, yet there is disagreement regarding whether people who live and work in prisons should be prioritised in national vaccination programmes. To help resolve this, we critically examine the extent, nature, and quality of extant literature regarding prioritisation of COVID-19 vaccinations for people who live and work in prisons.

Using a scoping review as our methodological framework, we conducted a systematic literature search of 17 databases. From 2,307 potentially eligible articles, we removed duplicates and screened titles and abstracts to retain 45 articles for review and quality appraisal.

Findings indicated that while most countries recognise that prisons are at risk of high levels of COVID-19 transmission, only a minority have explicitly prioritised people who live and work in prisons for COVID-19 vaccination. Even among those that have, prioritisation criteria varies considerably. This is set against a backdrop of political barriers, such as politicians questioning the moral deservingness of people in prison; policy barriers, such as the absence of a unified international framework of how vaccine prioritisation should proceed in prisons; logistical barriers regarding vaccine administration in prisons; and behavioural barriers including vaccine hesitancy.

We outline five strategies to prioritise people who live and work in prisons in COVID-19 vaccination plans: (1) improving data collection on COVID-19 vaccination, (2) reducing the number of people imprisoned, (3) tackling vaccine populism through advocacy, (4) challenging arbitrary prioritisation processes via legal processes, and (5) conducting more empirical research on COVID-19 vaccination planning, delivery, and acceptability. Implementing these strategies would help to reduce the impact of COVID-19 on the prison population, prevent community transmission, improve vaccine uptake in prisons beyond the current pandemic, foster political accountability, and inform future decision-making.
Predicting Transdiagnostic Social Impairments in Childhood using Connectome-based Predictive Modeling
Authors: Dufford Alexander J. , Kimble Violet , Tejavibulya Link , Dadashkarimi Javid , Ibrahim Karim , Sukhodolsky Denis G. , Scheinost Dustin
Published: April 2022

Background

Social impairments are core features of multiple neurodevelopmental disorders. Previous neuroimaging studies have focused on elucidating associations between brain function and social impairments within disorders but have not predicted these impairments from brain connectivity in a transdiagnostic manner, across several diagnostic categories. This study used a machine learning approach to examine functional connectivity that predicts elevated social impairments in a transdiagnostic sample of youths. We hypothesized that predictive edges would be from brain regions involved in social cognition.

Methods

Connectome-based predictive modeling (CPM) was used to build a transdiagnostic model of social impairments as measured by the Social Responsiveness Scale (SRS-2, raw score >75). We used functional connectivity data during a social movie-watching task from the Healthy Brain Network data (N=144, mean age=11.68 (3.52), 32% male). The average number of diagnoses was 3.4 (SD = 1.82, range = 0–11), including ASD (40.9%), ADHD (79%), mood disorders (15.9%), and anxiety disorders (43%). A similar transdiagnostic sample high SRS-2 scores (n=41) was used for replication.

Result

SRS-2 scores were predicted from functional connectivity data using both 10-fold cross-validation (median q2=0.32, r=0.57, p<.001) and leave-one-group-out cross-validation (median q2’s>0.04, r’s>0.36, p’s<.001). Predictive connections were widely distributed across the brain but were rooted in regions involved in social cognition, the subcortex, and the salience network. The model successfully predicted SRS-2 scores in the replication sample (r=0.33, p<.035, df=39).

Conclusion

We identified connectivity patterns predictive of social impairments in a transdiagnostic sample. These networks have the potential to provide insight into development novel targeted interventions for social impairments across traditional diagnostic categories.
Correlations between kidney and heart function bioindicators and the expressions of Toll-Like, ACE2, and NRP-1 receptors in COVID-19
Authors: Sultan Rabab Hussain , Abdallah Maged , Ali Tarek Mohamed , Assal Hebatallah Hany , Ahmed Amr E. , Elesawy Basem H , Ahmed Osama M.
Published: April 2022

Background

COVID-19 impacts the cardiovascular system resulting in myocardial damage and also affects the kidneys leading to renal dysfunction. This effect is mostly through the binding with angiotensin-converting enzyme-2 (ACE2) and Neuropilin-1(NRP-l) receptors. Toll-Like Receptors (TLRs) typically combine with microbial pathogens and provoke an inflammatory response.

Aim

This work aims to compare the changes in kidney and heart function bioindicators and expressions of TLRs (TLR2 and TLR2) as well as ACE2 and NRP-l receptors in moderate and severe COVID-19 patients. The correlations between kidney and heart function bioindicators and expressions of these receptors are also studied.

Patients and Methods

In this study, 50 healthy control and 100 COVID-19 patients (55 male and 45 female) were enrolled. According to WHO guidelines, these participants were divided into severe (50 cases) and moderate (50 cases). Serum creatinine, blood urea, CKMB, LDH, and Troponin I were estimated. We measured the gene expression for Toll-Like Receptors (TLR2, TLR4), ACE2, and NRP-1 in the blood samples using quantitative real-time PCR (qRT -PCR).

Results

In comparison with the healthy group, all patients exhibited a significant elevation in the serum creatinine, blood urea, cardiac enzymes, and CRP. As well, all studied patients revealed a significant elevation in the expression levels of TLR2, TLR4, ACE2, and NRP-1 mRNA. In all patients, CKMB, ACE2, and NRP-1 mRNA expression levels were positively correlated to both TLR2 and TLR4 expression levels. Moreover, serum creatinine and blood urea were positively correlated to both TLR2 and TLR 4 expression levels in the severe group only.

Conclusions

Our study concluded that expression levels for TLR2, TLR4, ACE2, and NRP-1 mRNA in both severe and moderate patients were positively correlated with renal biomarkers and cardiac enzymes. Innate immune markers can be important because they correlate with the severity of illness in COVID-19.
Right hemispheric white matter hyperintensities improve the prediction of spatial neglect severity in acute stroke
Authors: Röhrig Lisa , Sperber Christoph , Bonilha Leonardo , Rorden Christopher , Karnath Hans-Otto
Published: April 2022

White matter hyperintensities (WMH) are frequently observed in brain scans of elderly people. They are associated with an increased risk of stroke, cognitive decline, and dementia. However, it is unknown yet if measures of WMH provide information that improve the understanding of poststroke outcome compared to only state-of-the-art stereotaxic structural lesion data. We implemented high-dimensional machine learning models, based on support vector regression (SVR), to predict the severity of spatial neglect in 103 acute right hemispheric stroke patients. We found that (1) the additional information of right hemispheric voxel-based topographic WMH extent indeed yielded an improvement in predicting acute neglect severity (compared to the voxel-based stroke lesion map alone). (2) Periventricular WMH appeared more relevant for prediction than deep subcortical WMH. (3) Among different WMH measures, voxel-based maps as measures of topographic extent allowed more accurate predictions compared to the use of traditional ordinally assessed visual rating scales (Fazekas scale, Cardiovascular Health Study scale). In summary, topographic WMH appears to be a valuable clinical imaging biomarker for predicting the severity of cognitive deficits and bears great potential for rehabilitation guidance of acute stroke patients.
A cross-sectional study of the commercial plant-based landscape across the US, UK and Canada
Authors: Guess Nicola , Klatt Kevin , Wei Dorothy , Williamson Eric , Ulgenalp Ilayda , Trinidade Ornella , Kusaslan Eslem , Yilidrim Azize , Gowers Charlotte , Guard Robert , Mills Chris
Published: April 2022

As plant-based foods comprise an ever-increasing proportion of the diet, understanding the nutritional composition of these products is critical. In this study we assess the nutritional content of all commercial plant-based products across multiple sectors (supermarkets, fast food & sit down restaurants, food delivery companies and manufacturers) in the US, UK and Canada. We identified 3488 unique products. Across all sectors, 45% of main meals had >15g protein, 60% had <10%kcal from saturated fat; 29% had >10g fibre per meal; 86% had <1000mg sodium. At restaurants, meat-based main meals were significantly higher in protein and sodium compared to vegetarian and vegan meals. The meat-based options were also significantly higher in saturated fat than the vegan but not vegetarian options. We conclude that plant-based items tend to be lower in saturated fat and sodium than their meat-based counterparts but improvements are needed to optimise their nutritional composition.
wenda_gpu: fast domain adaptation for genomic data
Authors: Hippen Ariel A. , Crawford Jake , Gardner Jacob R. , Greene Casey S.
Published: April 2022

Motivation

Domain adaptation allows for development of predictive models even in cases with limited sample data. Weighted elastic net domain adaptation specifically leverages features of genomic data to maximize transferability but the method is too computationally demanding to apply to many genome-sized datasets.

Results

We developed wenda_gpu, which uses GPyTorch to train models on genomic data within hours on a single GPU-enabled machine. We show that wenda_gpu returns comparable results to the original wenda implementation, and that it can be used for improved prediction of cancer mutation status on small sample sizes than regular elastic net.

Availability

wenda_gpu is available on GitHub at https://github.com/greenelab/wenda_gpu/.

Contact

casey.s.greene@cuanschutz.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Germline variants associated with immunotherapy-related adverse events
Authors: Groha Stefan , Alaiwi Sarah Abou , Xu Wenxin , Naranbhai Vivek , Nassar Amin H. , Bakouny Ziad , Adib Elio , Nuzzo Pier V. , Schmidt Andrew L. , Labaki Chris , Zarif Talal El , Ricciuti Biagio , Alessi Joao Victor , Braun David A. , Shukla Sachet A. , Keenan Tanya E. , Van Allen Eliezer , Awad Mark M. , Manos Michael , Rahma Osama , Zubiri Leyre , Villani Alexandra-Chloe , Hammer Christian , Khan Zia , Reynolds Kerry , Semenov Yevgeniy , Schrag Deborah , Kehl Kenneth L. , Freedman Matthew L. , Choueiri Toni K. , Gusev Alexander
Published: April 2022

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses in patients across multiple cancer types, but often lead to immune related adverse events (irAEs). Although a germline cause for irAEs has been hypothesized, no systematic genome wide association study (GWAS) has been performed and no individual variants associated with the overall likelihood of developing irAEs have yet been identified. We carried out a Genome-Wide Association Study (GWAS) of 1,751 patients on ICIs across 12 cancer types, with replication in an independent cohort of 196 patients and independent clinical trial data from 2275 patients. We investigated two irAE phenotypes: (i) high-grade (3-5) events defined through manual curation and (ii) all detectable events (including high-grade) defined through electronic health record (EHR) diagnosis followed by manual confirmation. We identified three genome-wide significant associations (p<5×10−8) in the discovery cohort associated with all-grade irAEs: rs16906115 near IL7 (combined p=1.6×10−11; hazard ratio (HR)=2.1), rs75824728 near IL22RA1 (combined p=6.6×10−9; HR=1.9), and rs113861051 on 4p15 (combined p=1.3×10−8, HR=2.0); with rs16906115 replicating in two independent studies. The association near IL7 colocalized with the gain of a novel cryptic exon for IL7, a critical regulator of lymphocyte homeostasis. Patients carrying the IL7 germline variant exhibited significantly increased lymphocyte stability after ICI initiation than non-carriers, and this stability was predictive of downstream irAEs and improved survival.
Distinguishing Lewy Body Dementia from Alzheimer’s Disease using Machine Learning on Heterogeneous Data: A Feasibility Study
Authors: McCombe Niamh , Joshi Alok , Finn David P. , McClean Paula L. , Roberts Gemma , O’Brien John T. , Thomas Alan J. , Kane Joseph P.M. , Wong-Lin KongFatt
Published: April 2022

Dementia with Lewy Bodies (DLB) is the second most common form of dementia, but diagnostic markers for DLB can be expensive and inaccessible, and many cases of DLB are undiagnosed. This work applies machine learning techniques to determine the feasibility of distinguishing DLB from Alzheimer’s Disease (AD) using heterogeneous data features. The Repeated Incremental Pruning to Produce Error Reduction (RIPPER) algorithm was first applied using a Leave-One-Out Cross-Validation protocol to a dataset comprising DLB and AD cases. Then, interpretable association rule-based diagnostic classifiers were obtained for distinguishing DLB from AD. The various diagnostic classifiers generated by this process had high accuracy over the whole dataset (mean accuracy of 94%). The mean accuracy in classifying their out-of-sample case was 80.5%. Every classifier generated consisted of very simple structure, each using 1-2 classification rules and 1-3 data features. As a group, the classifiers were heterogeneous and used several different data features. In particular, some of the classifiers used very simple and inexpensive diagnostic features, yet with high diagnostic accuracy. This work suggests that opportunities may exist for incorporating accessible diagnostic assessments while improving diagnostic rate for DLB.

Clinical Relevance

Simple and interpretable high-performing machine learning algorithms identified a variety of readily available clinical assessments for differential diagnosis of dementia, offering the opportunities to incorporate various simple and inexpensive screening tests for DLB and addressing the problem of DLB underdiagnosis.
Efficient evolution of human antibodies from general protein language models and sequence information alone
Authors: Hie Brian L. , Xu Duo , Shanker Varun R. , Bruun Theodora U.J. , Weidenbacher Payton A. , Tang Shaogeng , Kim Peter S.
Published: April 2022

Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could accelerate artificial evolution. Here, we report that deep learning algorithms known as protein language models can evolve human antibodies with high efficiency, despite providing the models with no information about the target antigen, binding specificity, or protein structure, and also requiring no additional task-specific finetuning or supervision. We performed language-model-guided affinity maturation of seven diverse antibodies, screening 20 or fewer variants of each antibody across only two rounds of evolution. Our evolutionary campaigns improved the binding affinities of four clinically relevant antibodies up to 7-fold and three unmatured antibodies up to 160-fold across diverse viral antigens, with many designs also demonstrating improved thermostability and viral neutralization activity. Notably, our algorithm requires only a single wildtype sequence and computes recommended amino acid changes in less than a second. Moreover, the same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, indicating that these results generalize to many natural settings. Contrary to prevailing notions of evolution as difficult and resource-intensive, our results suggest that when constrained to a narrow manifold of evolutionary plausibility, evolution can become much easier, which we refer to as the “efficient manifold hypothesis.”
Symbiosis between Patescibacteria and Archaea discovered in wastewater-treating bioreactors
Authors: Kuroda Kyohei , Yamamoto Kyosuke , Nakai Ryosuke , Hirakata Yuga , Kubota Kengo , Nobu Masaru K. , Narihiro Takashi
Published: April 2022

Each prokaryotic domain, Bacteria and Archaea, contains a large and diverse group of organisms characterized with ultrasmall cell size and symbiotic lifestyles – Patescibacteria (also known as Candidate Phyla Radiation/CPR) and DPANN archaea. Cultivation-based approaches have revealed that Patesibacteria and DPANN symbiotically interact with bacterial and archaeal partners/hosts respectively, but cross-domain symbiosis/parasitism has never been observed. Here, we discovered physical interaction between ultramicrobacterial Patescibacteria and methanogenic archaea using cultures from anaerobic wastewater treatment sludge. In the cultures, we observed physical attachment of ultramicrobial cells to cells resembling Methanothrix and Methanospirillum using transmission electron microscopy and successfully detected physical association of Ca. Yanofskybacteria and Methanothrix using fluorescence in situ hybridization (FISH) (other ultramicrosized bacterial cells, presumably Patescibacteria, were also observed to attach on Methanospirillum). This was further confirmed to be a symbiosis rather than simple aggregation based on the observation that most ultramicrobacterial cells attached to Methanothrix were Ca. Yanofskybacteria and positive correlation (p < 0.05) between the relative abundance of Patescibacteria lineages and methanogenic archaea (e.g., Ca. Yanofskybacteria–Methanothrix and uncultured clade 32-520–Methanospirillum). The results shed light on a novel cross-domain symbiosis and inspire potential strategies for culturing CPR/DPANN.
Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual
Authors: Halfmann Peter J. , Minor Nicholas R. , Haddock Luis A. , Maddox Robert , Moreno Gage K. , Braun Katarina M. , Baker David A. , Riemersa Kasen K. , Prasad Ankur , Alman Kirsten J. , Lambert Matthew C. , Florek Kelsey , Bateman Allen , Westergaard Ryan , Safdar Nasia , Andes Dave R. , Kawaoka Yoshihiro , Fida Madiha , Yao Joseph D. , Friedrich Thomas C. , O’Connor David H.
Published: April 2022

Prolonged infections in immunocompromised individuals may be a source for novel SARS-CoV-2 variants, particularly when both the immune system and antiviral therapy fail to clear the infection, thereby promoting adaptation. Here we describe an approximately 16-month case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individual’s virus was resistant to this antibody via a globally unique Spike amino acid variant (E484T) that evolved from E484A earlier in infection. With the emergence and spread of the Omicron Variant of Concern, which also contains Spike E484A, E484T may arise again as an antibody-resistant derivative of E484A.
Cross-tissue meta-analysis of blood and brain epigenome-wide association studies in Alzheimer’s disease
Authors: Silva Tiago C. , Young Juan I. , Zhang Lanyu , Gomez Lissette , Schmidt Michael A. , Varma Achintya , Chen X. Steven , Martin Eden R. , Wang Lily
Published: April 2022

We performed a meta-analysis of two large independent blood-based Alzheimer’s disease (AD) epigenome-wide association studies, the ADNI and AIBL studies, and identified 5 CpGs, mapped to the SPIDR, CDH6 genes, and intergenic regions, that were significantly associated with AD diagnosis. A cross-tissue analysis that combined these blood DNA methylation datasets with four additional methylation datasets prioritized 97 CpGs and 10 genomic regions that are significantly associated with both AD neuropathology and AD diagnosis. Our integrative analysis revealed expressions levels of 13 genes and 10 pathways were significantly associated with the AD-associated methylation differences in both brain and blood, many are involved in the immune responses in AD, such as the CD79A, LY86, SP100, CD163, CD200, and MS4A1 genes and the neutrophil degranulation, antigen processing and presentation, interferon signaling pathways. An out-of-sample validation using the AddNeuroMed dataset showed the best performing logistic regression model included age, sex, cell types and methylation risk score based on prioritized CpGs from cross-tissue analysis (AUC = 0.696, 95% CI: 0.616 - 0.770, P-value = 2.78 × 10−5). Our study provides a valuable resource for future mechanistic and biomarker studies in AD.
Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization in Mexico: A nation-wide registry of seven COVID-19 vaccines
Authors: García-Grimshaw Miguel , Galnares-Olalde Javier Andrés , Bello-Chavolla Omar Yaxmehen , Michel-Chávez Anaclara , Cadena-Fernández Arturo , Briseño-Godínez María Eugenia , Antonio-Villa Neftali Eduardo , Nuñez Isaac , Gutiérrez-Romero Alonso , Hernández-Vanegas Laura , del Mar Saniger-Alba María , Carrillo-Mezo Roger , Ceballos-Liceaga Santa Elizabeth , Carbajal-Sandoval Guillermo , Flores-Silva Fernando Daniel , Díaz-Ortega José Luis , López-Gatell Hugo , Cortes-Alcalá Ricardo , Pérez-Padilla José Rogelio , Chiquete Erwin , Reyes-Terán Gustavo , Arauz Antonio , Valdés-Ferrer Sergio Iván
Published: April 2022

Background

Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 has been linked to a few (ChAdOx1 nCov-19 and Ad26.COV2-S), but not all vaccines, including mRNA-based ones. Epidemiological information on GBS among recipients of other SARS-CoV-2-directed vaccines among Latinx/Hispanic recipients is scarce.

Methods

We report GBS incidence per million administered doses from a nationwide Mexican retrospective registry of adult (≥18 years) recipients of 81,842,426 doses of seven vaccines against SARS-CoV-2 immunized between December 24, 2020, and October 29, 2021. Cases were collected through a passive epidemiological surveillance system and defined as events occurring within 42 days from immunization. Vaccines were analyzed individually and by vector as either mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), or inactivated whole-virion-vectored (CoronaVac).

Findings

We identified 97 patients (52 [53.6%] males; median age 44 years (interquartile range 33–60), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97–1.45), higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50–9.93) and BNT162b2 (1.92/1,00,000 doses, 95% CI 1.36–2.71) recipients. The overall interval from vaccination-to-GBS symptoms onset was 10 days (interquartile range 3–17). Preceding diarrhea (≤ 4 weeks) was reported in 21.6%, and four (4.1%) more had mild COVID-19. Only 18 patients were tested for Campylobacter jejuni infection; 16 (88.9%) were positive. Electrophysiological examinations were performed in 76 (78.4%) patients (axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar between platforms. On initial evaluation, 91.8% had a GBS disability score ≥ 3. Seventy-five (77.3%) patients received intravenous immunoglobulin, seven (7.2%) plasma exchanges, and 15 (15.5%) were treated conservatively. There were 10 (10.3%) deaths, and 79.1% of survivors were unable to walk independently at discharge.

Interpretation

In our population, GBS was an infrequent AEFI, observed in less than 1.2/1,000,000 administered doses of vaccines against SARS-CoV-2. Observed incidences were higher among Ad26.COV2.S and BNT162b2 recipients individually and for mRNA-vectored vaccines as a group.
Investigating the Consistency of Extracellular Vesicle Production from Breast Cancer Subtypes Using CELLine Adherent Bioreactors
Authors: Hisey Colin L. , Artuyants Anastasiia , Guo George , Chang Vanessa , Reshef Gabrielle , Middleditch Martin , Jacob Bincy , Chamley Lawrence W. , Blenkiron Cherie
Published: April 2022

Extracellular vesicle (EV) research has grown rapidly in recent years, largely due to the potential use of EVs as liquid biopsy biomarkers or therapeutics. However, in-depth characterisation and validation of EVs produced using conventionalin vitrocultures can be challenging due to the large area of cell monolayers and volumes of culture media required. To overcome this obstacle, multiple bioreactor designs have been tested for EV production with varying success, but the consistency of EVs produced over time in these systems has not been reported previously. In this study, we demonstrate that several breast cancer cell lines of different subtypes can be cultured simultaneously in space, resource, and time efficient manner using CELLine AD 1000 systems, allowing the consistent production of vast amounts of EVs for downstream experimentation. We report an improved workflow used for inoculating, maintaining, and monitoring the bioreactors, their EV production, and the characterisation of the EVs produced. Lastly, our proteomic analyses of the EVs produced throughout the lifetime of the bioreactors show that core EV-associated proteins are relatively consistent, with few minor variations over time, and that tracking the production of EVs may be a convenient method for indirectly monitoring the bioreactors’ health. These findings will aid future studies requiring the simultaneous production of large amounts of EVs from several cell lines of different subtypes of a disease and other EV biomanufacturing applications.
A genetic and linguistic analysis of the admixture histories of the islands of Cabo Verde
Authors: Laurent Romain , Szpiech Zachary A. , da Costa Sergio S. , Thouzeau Valentin , Fortes-Lima Cesar A. , Dessarps-Freichey Françoise , Lémée Laure , Utgé José , Rosenberg Noah A. , Baptista Marlyse , Verdu Paul
Published: April 2022

From the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals’ birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants’ genomic diversity and structure on both sides of the Atlantic.
Modeling tactile pleasantness across skin types at the individual level reveals a reliable and stable basic function
Authors: Crucianelli Laura , Chancel Marie , Ehrsson H. Henrik
Published: April 2022

Touch is perceived most pleasant when delivered at velocities known to optimally activate C Tactile afferents. At the group level, pleasantness ratings of touch delivered at velocities in the range 0.3-30 cm/s follows an inverted-U shape curve, with maximum pleasantness between 1 and 10 cm/s. However, the prevalence, reliability, and stability of this function at the individual level and across skin types remains unknown. Here, we tested a range of seven velocities delivered with a soft brush, on both hairy and non-hairy skin in 123 participants. We showed that the relationship between pleasantness and velocity of touch is significantly best described by a negative quadratic model at the individual level in the majority of participants both on hairy (67.1%) and non-hairy skin (62.6%). Higher interoceptive accuracy and self-reported depression were related to a better fit of the quadratic model and to the steepness of the curve, respectively. The prevalence of the quadratic model was stable across body sites (62.6%), across two experimental sessions (73-78%,), and regardless of the number of trials. Thus, the individual perception of tactile pleasantness follows a characteristic velocity-dependent function across skin types and shows trait characteristics, making it a possible biomarker for mental health disorders.