bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of comorbidities in patients with diffuse peritonitis
Authors: Špička Petr , Chudáček Josef , Řezáč Tomáš , Vomáčková Katherine , Ambrož Radek , Molnár Ján , Klos Dušan , Vrba Radek
Published: October 2022

Background

Diffuse peritonitis is a severe disease with high mortality and morbidity rates. Therapy is fundamentally surgical. It is important to identify patients with a significantly worse prognosis and patients who may benefit from more aggressive surgical and postsurgical care such as NPWT (Narrow Pressure Wound Therapy) prior to surgery. We tried to identify a determining factor for higher morbidity and mortality rates resulting in a worse prognosis among initial data and patient comorbidities in order to focus therapy towards more aggressive surgical management.

Methods

In a group of 274 patients with diffuse peritonitis, we evaluated the type of peritonitis according to effusion, origin, surgery type, and the age, gender, and present comorbidities of the patients, and compared it with the overall mortality, morbidity rate, and duration of hospitalization.

Results

Patients without comorbidities had a significantly lower burden in both morbidity and mortality. We recorded the highest difference in mortality in patients with two or more comorbidities, with pulmonary and cardiovascular diseases, with malignancy and hypertension. Morbidity was found to be significantly exacerbated by the presence of two or more severe diseases, cardiovascular disease, malignancy, and hypertension.

Conclusion

We identified age, effusion type, and the presence of comorbidities as key factors for the prognosis of our patients—the morbidity and mortality rates were substantially increased in patients with two or more comorbidities, as well as by the presence of cardiovascular disease, malignancy, and hypertension. A more aggressive approach should be considered to improve the prognosis in these patients.
Numerical Analysis of Thermoplastically Welded CFRP Structures
Authors: Kreikemeier J. , Abdulkadir A.
Published: October 2022

Carbon fibre reinforced thermoplastic polymers (CFRTP) are of particular interest to the aerospace industry. The possibility of thermoplastic welding as a joining method makes CFRTP an enabler in the pre-installation of systemic functionalities and cabin elements. This can be achieved by dust-free joining. In this work, thermoplastically welded joining zones are numerically analysed and evaluated for their failure behaviour. Finite element models for the evaluation of the peel strength (L-pull) are defined. In particular, the respective beginning of the damage as well as the damage propagation within the thermoplastic joining zone are of interest in order to identify the critical regions and to derive possibilities for design improvements.
Optimal climate policies under fairness preferences
Authors: Rogna Marco , Vogt Carla J.
Published: October 2022

Integrated assessment models are tools largely used to investigate the benefit of reducing polluting emissions and limiting the anthropogenic mean temperature rise. However, they have been often criticized for their underlying assumptions, often leading to low levels of abatement. Countries and regions that are generally the actors in these models are usually depicted as having standard concave utility functions in consumption. This, however, disregards a potentially important aspect of environmental negotiations, namely its distributive implications. The present paper tries to fill this gap assuming that countries/regions have Fehr and Schmidt (The Quarterly Journal of Economics114(3):817–868, 1999) (F&S) utility functions, specifically tailored for including inequality aversion. By adopting the RICE model, we compare its standard results with the ones obtained introducing F&S utility functions, showing that, under optimal cooperation, the level of temperature rise is lower in the last scenario. In particular, the peak temperature, reached in 2155 under standard assumptions and one or two decades later under F&S preferences with, respectively, heterogeneous and homogeneous F&S inequality aversion parameters (αand β), is of 2.86∘C in the former scenario and of 2.65∘C and 2.67∘C in the latter two. Furthermore, it is shown that potentially stable coalitions are easier to be achieved when F&S preferences are assumed. However, potentially stable coalitions are far from reaching environmental targets close to limiting the mean temperature rise below 2∘C despite the adoption of F&S utility functions. The 2∘C target is almost achieved in all scenarios when the payoffs in the F&S utility function are given by the per-capita consumption rather than utility of consumption, with F&S preferences and heterogeneous F&S inequality aversion parameters leading to a peak temperature rise of 2.04∘C.
Untangling connections between challenges in the adoption of learning analytics in higher education
Authors: Alzahrani Asma Shannan , Tsai Yi-Shan , Iqbal Sehrish , Marcos Pedro Manuel Moreno , Scheffel Maren , Drachsler Hendrik , Kloos Carlos Delgado , Aljohani Naif , Gasevic Dragan
Published: October 2022

Potential benefits of learning analytics (LA) for improving students’ performance, predicting students’ success, and enhancing teaching and learning practice have increasingly been recognized in higher education. However, the adoption of LA in higher education institutions (HEIs) to date remains sporadic and predominantly small in scale due to several socio-technical challenges. To better understand why HEIs struggle to scale LA adoption, it is needed to untangle adoption challenges and their related factors. This paper presents the findings of a study that sought to investigate the associations of adoption factors with challenges HEIs face in the adoption of LA and how these associations are compared among HEIs at different scopes of adoption. The study was based on a series of semi-structured interviews with senior managers in HEIs. The interview data were thematically analysed to identify the main challenges in LA adoption. The connections between challenges and other factors related to LA adoption were analysed using epistemic network analysis (ENA). From senior managers’ viewpoints, ethical issues of informed consent and resistance culture had the strongest links with challenges of learning analytic adoption in HEI; this was especially true for those institutions that had not adopted LA or who were in the initial phase of adoption (i.e., preparing for or partially implementing LA). By contrast, among HEIs that had fully adopted LA, the main challenges were found to be associated with centralized leadership, gaps in the analytic capabilities, external stakeholders, and evaluations of technology. Based on the results, we discuss implications for LA strategy that can be useful for institutions at various stages of LA adoption, from early stages of interest to the full adoption phase.
Comparing approaches for selection, development, and deployment of extended reality (XR) teaching applications: A case study at The University of Newcastle Australia
Authors: Kluge Murielle G. , Maltby Steven , Kuhne Caroline , Evans Darrell J. R. , Walker Frederick Rohan
Published: October 2022

The use of extended reality (XR) technology in education offers many advantages for transferring knowledge and practical skills training at the higher education level. As a result, many Universities over the past 5 + years have undertaken pilot programs to both develop XR content and assess how to best implement it within existing teaching and learning systems. Unfortunately, very few of these efforts have included structured evaluation or documentation. As such, limited published evidence exists to inform processes and approaches that may assist or hinder broad scale implementation. This leads many Universities to unnecessarily commit significant time and resources to testing identical or similar approaches, resulting in repeated identification of the same or similar challenges. In response to this situation, The University of Newcastle, Australia decided to systematically document the approach for selection, development and implementation of four new virtual-reality (VR) teaching applications. The current paper contains a detailed intrinsic case study, outlining the process and critical elements that shaped the selection of suitable teaching content, software development, hardware solutions and implementation. Details are provided on how decisions were made, what components were considered helpful, challenges identified, and important lessons outlined. These findings will be useful to organisations and individuals as they look to develop pathways and processes to integrate XR technology, particularly within their existing training and educational frameworks.
Revisiting and interpreting the role of female dominance in male mate choice: the importance of replication in ecology and evolution
Authors: Harrison Lauren M. , Jennions Michael D.
Published: October 2022

In many species females prefer to mate with socially dominant males, often because it elevates their fecundity by providing greater access to material resources or lowers offspring mortality due to superior male defence. Far fewer studies have tested whether males prefer socially dominant females. Intriguingly, an earlier study showed that when the sexes freely interact, male mosquitofish (Gambusia holbrooki) preferentially attempt to mate with dominant females. Here we replicate this study using a slightly modified experimental design to test the generality of its finding. In addition, we conducted standard, two-choice male mate choice trials to test directly whether males prefer dominant over subordinate females. Corroborating the previous study, we found that when a male and two females freely interact, males more often attempt to mate with the dominant female. However, males did not prefer to associate with (i.e., choose) dominant females in two-choice trials where females could not interact. We discuss whether greater access to males is a benefit of female social dominance, or an epiphenomenon of other benefits of dominance.
How Many Small Agglomerations Do Exist in the European Union, and How Should We Treat Their Wastewater?
Authors: Pistocchi Alberto , Parravicini Vanessa , Langergraber Guenter , Masi Fabio
Published: October 2022

The European Union (EU)’s legislation on urban wastewater requires all agglomerations with a population equivalent (PE) above 2000 people to undergo a secondary (mechanical/physical and biological) wastewater treatment. Agglomerations below 2000 PE, though, fall outside the scope of the current EU’s legislation. As such, their regulation is heterogeneous across the various EU member states, and there is no systematic collection nor reporting of data enabling an estimation of their actual significance as a source of pollution for the receiving water bodies. Here we present a spatial model to delineate agglomerations in a GIS, based on population distribution and land cover. From the model results, in the EU, we identify 364,650 agglomerations with 2000 PE or less, housing a cumulative population of about 75 million inhabitants. We then calculate the organic matter and nutrient loads these agglomerations can discharge, assuming they presently undergo primary wastewater treatment, and the reduction of loads that can be expected under different treatment scenarios, together with the corresponding treatment costs based on a simple cost model. Using a conventional shadow price for the organic matter and nutrients removed, we show that all treatment scenarios show a benefit-to-cost ratio (B/C) above (or close to) 1. However, only a scenario of secondary treatment applied to all agglomerations above 1000 PE provides sufficient safety margins on the B/C. This suggests the opportunity to expand the scope of the current legislation down to agglomerations of this size, while addressing smaller agglomerations depending on their actual impacts on the receiving water bodies, through “appropriate treatments” defined by the local authorities.
Potential and limitations for monitoring of pesticide biodegradation at trace concentrations in water and soil
Authors: Aldas-Vargas Andrea , Poursat Baptiste A. J. , Sutton Nora B.
Published: October 2022

Pesticides application on agricultural fields results in pesticides being released into the environment, reaching soil, surface water and groundwater. Pesticides fate and transformation in the environment depend on environmental conditions as well as physical, chemical and biological degradation processes. Monitoring pesticides biodegradation in the environment is challenging, considering that traditional indicators, such as changes in pesticides concentration or identification of pesticide metabolites, are not suitable for many pesticides in anaerobic environments. Furthermore, those indicators cannot distinguish between biotic and abiotic pesticide degradation processes. For that reason, the use of molecular tools is important to monitor pesticide biodegradation-related genes or microorganisms in the environment. The development of targeted molecular (e.g., qPCR) tools, although laborious, allowed biodegradation monitoring by targeting the presence and expression of known catabolic genes of popular pesticides. Explorative molecular tools (i.e., metagenomics & metatranscriptomics), while requiring extensive data analysis, proved to have potential for screening the biodegradation potential and activity of more than one compound at the time. The application of molecular tools developed in laboratory and validated under controlled environments, face challenges when applied in the field due to the heterogeneity in pesticides distribution as well as natural environmental differences. However, for monitoring pesticides biodegradation in the field, the use of molecular tools combined with metadata is an important tool for understanding fate and transformation of the different pesticides present in the environment.

Graphical abstract
Modernist Literary Collaborations Between Women and Men
Authors: McDonald Russell
Published: October 2022

Major figures including W. B. Yeats, Marianne Moore, D. H. Lawrence, Ford Madox Ford, and Virginia Woolf viewed 'cross-sex' collaboration as a valuable, and often subversive, strategy for bringing women and men's differing perspectives into productive dialogue while harnessing the creative potential of gendered discord. This study is the first to acknowledge collaboration between women and men as an important part of the modernist effort to 'make it new.' Drawing on current methods from textual scholarship to read modernist texts as material, socially constructed products of multiple hands, the study argues that cross-sex collaboration involved writers working not just with each other, but also with publishers and illustrators. By documenting and tracing the contours of their desire for cross-sex collaboration, we gain a new understanding of the modernists' thinking about sex and gender relations, as well as three related topics of great interest to them: marriage, androgyny, and genius.
An analysis of human behaviour during aircraft evacuation situations using the AASK v3.0 database
Authors: Galea E. R. , Finney K. M. , Dixon A. J. P. , Siddiqui A. , Cooney D. P.
Published: October 2022

The Aircraft Accident Statistics and Knowledge (AASK) database is a repository of survivor accounts from aviation accidents. Its main purpose is to store observational and anecdotal data from the actual interviews of the occupants involved in aircraft accidents. The database has wide application to aviation safety analysis, being a source of factual data regarding the evacuation process. It is also key to the development of aircraft evacuation models such as airEXODUS, where insight into how people actually behave during evacuation from survivable aircraft crashes is required. This paper describes recent developments with the database leading to the development of AASK v3.0. These include significantly increasing the number of passenger accounts in the database, the introduction of cabin crew accounts, the introduction of fatality information, improved functionality through the seat plan viewer utility and improved ease of access to the database via the internet. In addition, the paper demonstrates the use of the database by investigating a number of important issues associated with aircraft evacuation. These include issues associated with social bonding and evacuation, the relationship between the number of crew and evacuation efficiency, frequency of exit/slide failures in accidents and exploring possible relationships between seating location and chances of survival. Finally, the passenger behavioural trends described in analysis undertaken with the earlier database are confirmed with the wider data set.
Velocity field path-planning for single and multiple unmanned aerial vehicles
Authors: McInnes C. R.
Published: October 2022

Unmanned aerial vehicles (UAV) have seen a rapid growth in utilisation for reconnaissance, mostly using single UAVs. However, future utilisation of UAVs for applications such as bistatic synthetic aperture radar and stereoscopic imaging, will require the use of multiple UAVs acting cooperatively to achieve mission goals. In addition, to de-skill the operation of UAVs for certain applications will require the migration of path-planning functions from the ground to the UAV. This paper details a computationally efficient algorithm to enable path-planning for single UAVs and to form and re-form UAV formations with active collision avoidance. The algorithm presented extends classical potential field methods used in other domains for the UAV path-planning problem. It is demonstrated that a range of tasks can be executed autonomously, allowing high level tasking of single and multiple UAVs in formation, with the formation commanded as a single entity.
Aerodynamic admittance of a two-dimensional body
Authors: Filippone A. , Siquier J.
Published: October 2022

The unsteady load response in the frequency domain for a general two-dimensional body has been determined. Systems with one degree of freedom have been considered. The theory is based on the potential incompressible flow, and resolves around a mathematical treatment that starts from the theory of Drischler and Diederich. Admittance for the lift force and pitching moment (or side force and yawing moment for non lifting systems) has been calculated in closed form or numerically for aerofoils, swept back and swept forward wings, delta wings, and some ground vehicles (various car shapes) using sinusoidal and square gusts. Simulations have been performed for a wide range of gust speed ratios. The general features of the admittance function are discussed. It is proved that for some geometries there is an large number of frequencies that yield critical damping. These frequencies are generally very high. Comparisons with existing experimental data are good in the whole range of practical frequencies.
Sinus, middle-ear and mastoid radiological findings of severe acute respiratory syndrome coronavirus-2
Authors: Watts E , Balai E , Kwatra D , Banerjee S , Hoskison E
Published: October 2022

Objective

To assess the incidence of radiological inflammation within the paranasal sinuses, middle ear and mastoid in patients with confirmed severe acute respiratory syndrome coronavirus-2.

Methods

A retrospective cohort study was conducted to examine consecutive adults (aged over 18 years) with coronavirus disease 2019 (confirmed on polymerase chain reaction within 7 days of imaging) who underwent computed tomography of the head between 1 March 2020 and 24 June 2020. Lund–Mackay and mastoid and middle-ear opacification scores were used to categorise the extent of sinus and mastoid opacification on axial and coronal computed tomography images.

Results

Of 147 patients originally identified, only 83 met the inclusion criteria. Sinus opacification was present in 51.8 per cent of patients (n = 43), and middle-ear or mastoid opacification was observed in 24.1 per cent (n = 20). There was no statistically significant difference in sinus or middle-ear and mastoid opacification between patients after stratification based on 30-day all-cause mortality.

Conclusion

Radiological computed tomography findings suggest mild mucosal disease within the sinuses, middle ear and mastoid. There was no statistical correlation between such opacification and 30-day mortality.
The Case of Proclamations (1610), Aldred's Case (1610), and the Origins of the Sic Utere/Salus Populi Antithesis
Authors: Morag-Levine Noga
Published: October 2022

At least since the middle of the eighteenth-century, salus populi (the people’s welfare) and sic utere (use your own without injuring others) have encapsulated alternative conceptions of regulatory power, with the former associated with continental police regimes and the latter with Anglo-American conceptions of limited government. This article finds the origins of this antithesis in the intersection of two landmark cases addressed by Coke in the fall of 1610: Aldred’s Case, sic utere’s foundational text, and the Case of Proclamations, where Coke disputed the legality of building and starch proclamations. The Crown had provided common-good justifications for these proclamations, but their beneficiaries had included the individual neighbors of smelly starch makers and obstructive new buildings who had been left unprotected by previously existing local law. Rather than acquiescing to centralized legislation enacted via proclamation or parliament, Coke hinted in Aldred’s Case towards common law nuisance adjudication based on the sic utere principle as the desired mechanism for overriding local law that had privileged injurious land uses. Like salus populi, sic utere served a centralizing function. But whereas the former invited expansive regulatory agendas, the latter conditioned interventions on a judicial finding of a nuisance. In this, Coke’s invocation of sic utere in Aldred’s Case presaged the maxim’s eventual role as a substantive limit on the police power.
“Do Not Harm the Decorum”: Mixed Courts and Cloth in Colonial Indonesia
Authors: Ravensbergen Sanne
Published: October 2022

In this article four photographs of mixed law courts (landraad) in nineteenth-century colonial Indonesia are approached as a window to study the materiality and meaning of cloth in courtrooms. The photos grant access to a careful colonial curation as well as complex Javanese hierarchies that were translated onto and through cloth, and its colors and patterns. Batik sarongs, tablecloths, head scarves, robes and gowns, coats and turbans reveal a courtroom of semiotic richness and plurality where different actors were signaling different messages to multiple audiences. This emphasis on cloth contributes to an emergent and rich discussion on the importance of objects in the study of law and empire, that has primarily focused on the materiality of paper and other objects of lawmaking. In the mixed court of the landraad, it was cloth that spoke louder than words and paper. This article emphasizes that in a mixed court the display of a plural world and jurisdictional layering, complicating the binary between direct and indirect colonial rule, was more important than a monolithic reflection of state law. Cloth was crucial to the display of this plural world and used as a way to impose, maintain, alter, insert oneself in or resist colonial rule.
An Application of a Runtime Epistemic Probabilistic Event Calculus to Decision-making in e-Health Systems
Authors: D’ASARO FABIO AURELIO , RAGGIOLI LUCA , MALEK SALIM , GRAZIOSO MARCO , ROSSI SILVIA
Published: October 2022

We present and discuss a runtime architecture that integrates sensorial data and classifiers with a logic-based decision-making system in the context of an e-Health system for the rehabilitation of children with neuromotor disorders. In this application, children perform a rehabilitation task in the form of games. The main aim of the system is to derive a set of parameters the child’s current level of cognitive and behavioral performance (e.g., engagement, attention, task accuracy) from the available sensors and classifiers (e.g., eye trackers, motion sensors, emotion recognition techniques) and take decisions accordingly. These decisions are typically aimed at improving the child’s performance by triggering appropriate re-engagement stimuli when their attention is low, by changing the game or making it more difficult when the child is losing interest in the task as it is too easy. Alongside state-of-the-art techniques for emotion recognition and head pose estimation, we use a runtime variant of a probabilistic and epistemic logic programming dialect of the Event Calculus, known as the Epistemic Probabilistic Event Calculus. In particular, the probabilistic component of this symbolic framework allows for a natural interface with the machine learning techniques. We overview the architecture and its components, and show some of its characteristics through a discussion of a running example and experiments.
The Key Factors Controlling the Seasonality of Planetary Climate
Authors: Guendelman Ilai , Kaspi Yohai
Published: October 2022

Several different factors influence the seasonal cycle of a planet. This study uses a general circulation model and an energy balance model (EBM) to assess the parameters that govern the seasonal cycle. We define two metrics to describe the seasonal cycle, ϕs, the latitudinal shift of the maximum temperature, and ΔT, the maximum seasonal temperature variation amplitude. We show that alongside the expected dependence on the obliquity and orbital period, where seasonality generally strengthens with an increase in these parameters, the seasonality depends in a nontrivial way on the rotation rate. While the seasonal amplitude decreases as the rotation rate slows down, the latitudinal shift, ϕs, shifts poleward. A similar result occurs in a diffusive EBM with increasing diffusivity. These results suggest that the influence of the rotation rate on the seasonal cycle stems from the effect of the rotation rate on the atmospheric heat transport.
Tunable High‐Resolution Synthetic Aperture Radar Imaging
Authors: Kim Arnold D. , Tsogka Chrysoula
Published: October 2022

We have recently introduced a modification of the multiple signal classification method for synthetic aperture radar. This method incorporates a user‐defined parameter, ϵ, that allows for tunable quantitative high‐resolution imaging. However, this method requires relatively large single‐to‐noise ratios (SNR) to work effectively. Here, we first identify the fundamental mechanism in that method that produces high‐resolution images. Then we introduce a modification to Kirchhoff Migration (KM) that uses the same mechanism to produce tunable, high‐resolution images. This modified KM method can be applied to low SNR measurements. We show simulation results that demonstrate the features of this method.
Light People: Professor Martin Booth spoke about adaptive optics and its applications
Authors: Cui Jiahe , He Chao , Chang Wei
Published: October 2022

Editorial

Adaptive optics (AO), a technique originally introduced by astronomers to correct for optical distortions when looking at distant stars, now benefits the entire optics and photonics society. Prof. Martin Booth, who leads his research lab at the University of Oxford where he started his career, was one of the first people to take advantage of AO for microscopy. Since then, he has been continuously promoting the wide application of AO in all aspects of biological research and material science. As one of the few people who has witnessed the growth of AO in various communities, Prof. Martin Booth talks about their major differences, as well as their current challenges and future development. He discusses how AO can benefit emerging areas and the key challenges that may be faced. Prof. Martin Booth has also been making continuous efforts in removing the barriers of AO so that it can be promoted towards the wider community. Finally, he shares his experience from actively taking up different roles in education and in various societies and provides valuable advice to all early career researchers on the wisdom of being successful in their future careers. It is an honour for us to invite Prof. Martin Booth on this issue, and to learn from his inspirations, enthusiasm, and dedication.
Validation of a multi-frequency bioelectrical impedance analysis device for the assessment of body composition in older adults with type 2 diabetes
Authors: Buch Assaf , Ben-Yehuda Arie , Rouach Vanessa , Maier Andrea B. , Greenman Yona , Izkhakov Elena , Stern Naftali , Eldor Roy
Published: October 2022

Background

Aging and type 2 diabetes (T2DM) are associated with an increased risk of sarcopenia. Diagnosis of sarcopenia is commonly done using dual-energy X-ray absorptiometry (DXA) in specialized settings. Another available method for assessing body composition is direct segmental multi-frequency bioelectrical impedance analysis (DSMF-BIA). Here, we examine the accuracy of a DSMF-BIA (InBody-770) for assessing body composition in older adults with T2DM when compared to DXA.

Methods

Eighty-four obese/overweight older adults (49 women, 71 ± 5 years) with T2DM who were recruited for the CEV-65 study and had both DSMF-BIA and DXA assessments at baseline were included. The analysis included Bland–Altman plots and intra class correlation coefficients. Sub-analyses were performed according to gender and following 10 weeks of interventions (diet, circuit training, and Empagliflozin).

Results

The leg lean mass results according to DSMF-BIA and DXA were 14.76 ± 3.62 kg and 15.19 ± 3.52 kg, respectively, with no difference between devices according to Bland–Altman analyses (p = 0.353). Assessment of appendicular skeletal mass index did not differ between DSMF-BIA and DXA (7.43 vs. 7.47 kg/m2; p = 0.84; ICC = 0.965, p < 0.0001; mean difference −0.068, p = 0.595). Gender and treatment interventions did not modify the accuracy of the DSMF-BIA when compared to DXA.

Conclusions

In older adults with T2DM the degree of agreement between DSMF-BIA and DXA, was high, supporting the use of DSMF-BIA to measure muscle mass.
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia
Authors: Herbst Sophie A. , Vesterlund Mattias , Helmboldt Alexander J. , Jafari Rozbeh , Siavelis Ioannis , Stahl Matthias , Schitter Eva C. , Liebers Nora , Brinkmann Berit J. , Czernilofsky Felix , Roider Tobias , Bruch Peter-Martin , Iskar Murat , Kittai Adam , Huang Ying , Lu Junyan , Richter Sarah , Mermelekas Georgios , Umer Husen Muhammad , Knoll Mareike , Kolb Carolin , Lenze Angela , Cao Xiaofang , Österholm Cecilia , Wahnschaffe Linus , Herling Carmen , Scheinost Sebastian , Ganzinger Matthias , Mansouri Larry , Kriegsmann Katharina , Kriegsmann Mark , Anders Simon , Zapatka Marc , Del Poeta Giovanni , Zucchetto Antonella , Bomben Riccardo , Gattei Valter , Dreger Peter , Woyach Jennifer , Herling Marco , Müller-Tidow Carsten , Rosenquist Richard , Stilgenbauer Stephan , Zenz Thorsten , Huber Wolfgang , Tausch Eugen , Lehtiö Janne , Dietrich Sascha
Published: October 2022

Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.
Rapid antibiotic susceptibility testing and species identification for mixed samples
Authors: Kandavalli Vinodh , Karempudi Praneeth , Larsson Jimmy , Elf Johan
Published: October 2022

Antimicrobial resistance is an increasing problem on a global scale. Rapid antibiotic susceptibility testing (AST) is urgently needed in the clinic to enable personalized prescriptions in high-resistance environments and to limit the use of broad-spectrum drugs. Current rapid phenotypic AST methods do not include species identification (ID), leaving time-consuming plating or culturing as the only available option when ID is needed to make the sensitivity call. Here we describe a method to perform phenotypic AST at the single-cell level in a microfluidic chip that allows subsequent genotyping by in situ FISH. By stratifying the phenotypic AST response on the species of individual cells, it is possible to determine the susceptibility profile for each species in a mixed sample in 2 h. In this proof-of-principle study, we demonstrate the operation with four antibiotics and mixed samples with combinations of seven species.
Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3
Authors: Georges Romain O. , Sepulveda Hugo , Angel J. Carlos , Johnson Eric , Palomino Susan , Nowak Roberta B. , Desai Arshad , López-Moyado Isaac F. , Rao Anjana
Published: October 2022

TET (Ten-Eleven Translocation) dioxygenases effect DNA demethylation through successive oxidation of the methyl group of 5-methylcytosine (5mC) in DNA. In humans and in mouse models, TET loss-of-function has been linked to DNA damage, genome instability and oncogenesis. Here we show that acute deletion of all three Tet genes, after brief exposure of triple-floxed, Cre-ERT2-expressing mouse embryonic stem cells (mESC) to 4-hydroxytamoxifen, results in chromosome mis-segregation and aneuploidy; moreover, embryos lacking all three TET proteins showed striking variation in blastomere numbers and nuclear morphology at the 8-cell stage. Transcriptional profiling revealed that mRNA encoding a KH-domain protein, Khdc3 (Filia), was downregulated in triple TET-deficient mESC, concomitantly with increased methylation of CpG dinucleotides in the vicinity of the Khdc3 gene. Restoring KHDC3 levels in triple Tet-deficient mESC prevented aneuploidy. Thus, TET proteins regulate Khdc3 gene expression, and TET deficiency results in mitotic infidelity and genome instability in mESC at least partly through decreased expression of KHDC3.
Engineered cell differentiation and sexual reproduction in probiotic and mating yeasts
Authors: Jensen Emil D. , Deichmann Marcus , Ma Xin , Vilandt Rikke U. , Schiesaro Giovanni , Rojek Marie B. , Lengger Bettina , Eliasson Line , Vento Justin M. , Durmusoglu Deniz , Hovmand Sandie P. , Al’Abri Ibrahim , Zhang Jie , Crook Nathan , Jensen Michael K.
Published: October 2022

G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. GPCRs comprise the largest class of cell surface receptors in eukaryotes, and for more than three decades the pheromone-induced mating pathway in baker’s yeast Saccharomyces cerevisiae has served as a model for studying heterologous GPCRs (hGPCRs). Here we report transcriptome profiles following mating pathway activation in native and hGPCR-signaling yeast and use a model-guided approach to correlate gene expression to morphological changes. From this we demonstrate mating between haploid cells armed with hGPCRs and endogenous biosynthesis of their cognate ligands. Furthermore, we devise a ligand-free screening strategy for hGPCR compatibility with the yeast mating pathway and enable hGPCR-signaling in the probiotic yeast Saccharomyces boulardii. Combined, our findings enable new means to study mating, hGPCR-signaling, and cell-cell communication in a model eukaryote and yeast probiotics.
Slow light in a 2D semiconductor plasmonic structure
Authors: Klein Matthew , Binder Rolf , Koehler Michael R. , Mandrus David G. , Taniguchi Takashi , Watanabe Kenji , Schaibley John R.
Published: October 2022

Spectrally narrow optical resonances can be used to generate slow light, i.e., a large reduction in the group velocity. In a previous work, we developed hybrid 2D semiconductor plasmonic structures, which consist of propagating optical frequency surface-plasmon polaritons interacting with excitons in a semiconductor monolayer. Here, we use coupled exciton-surface plasmon polaritons (E-SPPs) in monolayer WSe2 to demonstrate slow light with a 1300 fold decrease of the SPP group velocity. Specifically, we use a high resolution two-color laser technique where the nonlinear E-SPP response gives rise to ultra-narrow coherent population oscillation (CPO) resonances, resulting in a group velocity on order of 105 m/s. Our work paves the way toward on-chip actively switched delay lines and optical buffers that utilize 2D semiconductors as active elements.
Promiscuity of response regulators for thioredoxin steers bacterial virulence
Authors: Kim Ju-Sim , Born Alexandra , Till James Karl A. , Liu Lin , Kant Sashi , Henen Morkos A. , Vögeli Beat , Vázquez-Torres Andrés
Published: October 2022

The exquisite specificity between a sensor kinase and its cognate response regulator ensures faithful partner selectivity within two-component pairs concurrently firing in a single bacterium, minimizing crosstalk with other members of this conserved family of paralogous proteins. We show that conserved hydrophobic and charged residues on the surface of thioredoxin serve as a docking station for structurally diverse response regulators. Using the OmpR protein, we identify residues in the flexible linker and the C-terminal β-hairpin that enable associations of this archetypical response regulator with thioredoxin, but are dispensable for interactions of this transcription factor to its cognate sensor kinase EnvZ, DNA or RNA polymerase. Here we show that the promiscuous interactions of response regulators with thioredoxin foster the flow of information through otherwise highly dedicated two-component signaling systems, thereby enabling both the transcription of Salmonella pathogenicity island-2 genes as well as growth of this intracellular bacterium in macrophages and mice.
Genomic insights into the physiology of Quinella, an iconic uncultured rumen bacterium
Authors: Kumar Sandeep , Altermann Eric , Leahy Sinead C. , Jauregui Ruy , Jonker Arjan , Henderson Gemma , Kittelmann Sandra , Attwood Graeme T. , Kamke Janine , Waters Sinéad M. , Patchett Mark L. , Janssen Peter H.
Published: October 2022

Quinella is a genus of iconic rumen bacteria first reported in 1913. There are no cultures of these bacteria, and information on their physiology is scarce and contradictory. Increased abundance of Quinella was previously found in the rumens of some sheep that emit low amounts of methane (CH4) relative to their feed intake, but whether Quinella contributes to low CH4 emissions is not known. Here, we concentrate Quinella cells from sheep rumen contents, extract and sequence DNA, and reconstruct Quinella genomes that are >90% complete with as little as 0.20% contamination. Bioinformatic analyses of the encoded proteins indicate that lactate and propionate formation are major fermentation pathways. The presence of a gene encoding a potential uptake hydrogenase suggests that Quinella might be able to use free hydrogen (H2). None of the inferred metabolic pathways is predicted to produce H2, a major precursor of CH4, which is consistent with the lower CH4 emissions from those sheep with high abundances of this bacterium.
Epidemic spreading under mutually independent intra- and inter-host pathogen evolution
Authors: Zhang Xiyun , Ruan Zhongyuan , Zheng Muhua , Zhou Jie , Boccaletti Stefano , Barzel Baruch
Published: October 2022

The dynamics of epidemic spreading is often reduced to the single control parameter R0 (reproduction-rate), whose value, above or below unity, determines the state of the contagion. If, however, the pathogen evolves as it spreads, R0 may change over time, potentially leading to a mutation-driven spread, in which an initially sub-pandemic pathogen undergoes a breakthrough mutation. To predict the boundaries of this pandemic phase, we introduce here a modeling framework to couple the inter-host network spreading patterns with the intra-host evolutionary dynamics. We find that even in the extreme case when these two process are driven by mutually independent selection forces, mutations can still fundamentally alter the pandemic phase-diagram. The pandemic transitions, we show, are now shaped, not just by R0, but also by the balance between the epidemic and the evolutionary timescales. If mutations are too slow, the pathogen prevalence decays prior to the appearance of a critical mutation. On the other hand, if mutations are too rapid, the pathogen evolution becomes volatile and, once again, it fails to spread. Between these two extremes, however, we identify a broad range of conditions in which an initially sub-pandemic pathogen can breakthrough to gain widespread prevalence.
Combining mass spectrometry and machine learning to discover bioactive peptides
Authors: Madsen Christian T. , Refsgaard Jan C. , Teufel Felix G. , Kjærulff Sonny K. , Wang Zhe , Meng Guangjun , Jessen Carsten , Heljo Petteri , Jiang Qunfeng , Zhao Xin , Wu Bo , Zhou Xueping , Tang Yang , Jeppesen Jacob F. , Kelstrup Christian D. , Buckley Stephen T. , Tullin Søren , Nygaard-Jensen Jan , Chen Xiaoli , Zhang Fang , Olsen Jesper V. , Han Dan , Grønborg Mads , de Lichtenberg Ulrik
Published: October 2022

Peptides play important roles in regulating biological processes and form the basis of a multiplicity of therapeutic drugs. To date, only about 300 peptides in human have confirmed bioactivity, although tens of thousands have been reported in the literature. The majority of these are inactive degradation products of endogenous proteins and peptides, presenting a needle-in-a-haystack problem of identifying the most promising candidate peptides from large-scale peptidomics experiments to test for bioactivity. To address this challenge, we conducted a comprehensive analysis of the mammalian peptidome across seven tissues in four different mouse strains and used the data to train a machine learning model that predicts hundreds of peptide candidates based on patterns in the mass spectrometry data. We provide in silico validation examples and experimental confirmation of bioactivity for two peptides, demonstrating the utility of this resource for discovering lead peptides for further characterization and therapeutic development.
Climate-mediated shifts in temperature fluctuations promote extinction risk
Authors: Duffy Kate , Gouhier Tarik C. , Ganguly Auroop R.
Published: October 2022

Climate-mediated changes in thermal stress can destabilize animal populations and promote extinction risk. However, risk assessments often focus on changes in mean temperatures and thus ignore the role of temporal variability or structure. Using Earth System Model projections, we show that significant regional differences in the statistical distribution of temperature will emerge over time and give rise to shifts in the mean, variability and persistence of thermal stress. Integrating these trends into mathematical models that simulate the dynamical and cumulative effects of thermal stress on the performance of 38 globally distributed ectotherm species revealed complex regional changes in population stability over the twenty-first century, with temperate species facing higher risk. Yet despite their idiosyncratic effects on stability, projected temperatures universally increased extinction risk. Overall, these results show that the effects of climate change may be more extensive than previously predicted on the basis of the statistical relationship between biological performance and average temperature.
A high-throughput skim-sequencing approach for genotyping, dosage estimation and identifying translocations
Authors: Adhikari Laxman , Shrestha Sandesh , Wu Shuangye , Crain Jared , Gao Liangliang , Evers Byron , Wilson Duane , Ju Yoonha , Koo Dal-Hoe , Hucl Pierre , Pozniak Curtis , Walkowiak Sean , Wang Xiaoyun , Wu Jing , Glaubitz Jeffrey C. , DeHaan Lee , Friebe Bernd , Poland Jesse
Published: October 2022

The development of next-generation sequencing (NGS) enabled a shift from array-based genotyping to directly sequencing genomic libraries for high-throughput genotyping. Even though whole-genome sequencing was initially too costly for routine analysis in large populations such as breeding or genetic studies, continued advancements in genome sequencing and bioinformatics have provided the opportunity to capitalize on whole-genome information. As new sequencing platforms can routinely provide high-quality sequencing data for sufficient genome coverage to genotype various breeding populations, a limitation comes in the time and cost of library construction when multiplexing a large number of samples. Here we describe a high-throughput whole-genome skim-sequencing (skim-seq) approach that can be utilized for a broad range of genotyping and genomic characterization. Using optimized low-volume Illumina Nextera chemistry, we developed a skim-seq method and combined up to 960 samples in one multiplex library using dual index barcoding. With the dual-index barcoding, the number of samples for multiplexing can be adjusted depending on the amount of data required, and could be extended to 3,072 samples or more. Panels of doubled haploid wheat lines (Triticum aestivum, CDC Stanley x CDC Landmark), wheat-barley (T. aestivum x Hordeum vulgare) and wheat-wheatgrass (Triticum durum x Thinopyrum intermedium) introgression lines as well as known monosomic wheat stocks were genotyped using the skim-seq approach. Bioinformatics pipelines were developed for various applications where sequencing coverage ranged from 1 × down to 0.01 × per sample. Using reference genomes, we detected chromosome dosage, identified aneuploidy, and karyotyped introgression lines from the skim-seq data. Leveraging the recent advancements in genome sequencing, skim-seq provides an effective and low-cost tool for routine genotyping and genetic analysis, which can track and identify introgressions and genomic regions of interest in genetics research and applied breeding programs.