bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDBench: evaluating computational methods for protein-sequence design
Authors: Castorina Leonardo V , Petrenas Rokas , Subr Kartic , Wood Christopher W 
Published: January 2023

Abstract

Summary
Ever increasing amounts of protein structure data, combined with advances in machine learning, have led to the rapid proliferation of methods available for protein-sequence design. In order to utilize a design method effectively, it is important to understand the nuances of its performance and how it varies by design target. Here, we present PDBench, a set of proteins and a number of standard tests for assessing the performance of sequence-design methods. PDBench aims to maximize the structural diversity of the benchmark, compared with previous benchmarking sets, in order to provide useful biological insight into the behaviour of sequence-design methods, which is essential for evaluating their performance and practical utility. We believe that these tools are useful for guiding the development of novel sequence design algorithms and will enable users to choose a method that best suits their design target.

Availability and implementation
https://github.com/wells-wood-research/PDBench

Supplementary information
Supplementary data are available at Bioinformatics online.
Mapache: a flexible pipeline to map ancient DNA
Authors: Neuenschwander Samuel , Cruz Dávalos Diana I , Anchieri Lucas , Sousa da Mota Bárbara , Bozzi Davide , Rubinacci Simone , Delaneau Olivier , Rasmussen Simon , Malaspinas Anna-Sapfo 
Published: January 2023

Abstract

Summary
We introduce mapache, a flexible, robust and scalable pipeline to map, quantify and impute ancient and present-day DNA in a reproducible way. Mapache is implemented in the workflow manager Snakemake and is optimized for low-space consumption, allowing to efficiently (re)map large datasets—such as reference panels and multiple extracts and libraries per sample — to one or several genomes. Mapache can easily be customized or combined with other Snakemake tools.

Availability and implementation
Mapache is freely available on GitHub (https://github.com/sneuensc/mapache). An extensive manual is provided at https://github.com/sneuensc/mapache/wiki.

Supplementary information
Supplementary data are available at Bioinformatics online.
The association between atopic dermatitis, cognitive function and school performance in children and young adults
Authors: Vittrup Ida , Andersen Yuki M F , Skov Lone , Wu Jashin J , Agner Tove , Thomsen Simon F   , Egeberg Alexander , Thyssen Jacob P 
Published: January 2023

Abstract

Background
Children with atopic dermatitis (AD) may have disturbed sleep, affected self-esteem and decreased quality of life, likely interfering with performance in school.

Objectives
To examine the association between hospital-managed paediatric AD, school performance and cognitive function.

Methods
In this cross-sectional study we linked data from the Danish national registers and identified three populations between 2001 and 2019. Population 1 comprised children with graduation grades registered from lower secondary school, population 2 comprised adolescents with registration of an upper secondary graduation mean, and population 3 comprised male conscripts with registration of an IQ test score. AD was defined as a hospital diagnostic code (inpatient or outpatient) prior to the exam or conscription date, and was stratified according to severity, activity and atopic comorbidity. Outcomes included graduation mean from lower and upper secondary school, special educational assistance in primary and lower secondary school, and IQ at conscription.

Results
In total, 770 611 (12 137 with AD), 394 193 (6261 with AD) and 366 182 (4539 with AD) children and adolescents were included in populations 1 (lower secondary graduation), 2 (upper secondary graduation) and 3 (conscription), respectively. In lower secondary school, children with severe AD had significantly lower overall, written and oral graduation grade means compared with children with mild AD: respectively, difference −0.29 [95% confidence interval (CI) −0.45 to −0.13, P &lt; 0.001], difference −0.26 (95% CI −0.42 to −0.10, P = 0.0016) and difference −0.30 (95% CI −0.49 to −0.11, P = 0.0018). In upper secondary school, adolescents with AD performed similarly to their peers without AD. Young men with AD scored significantly lower IQ test means at conscription examination than male conscripts without AD: difference −0.60 (95% CI −0.87 to −0.32, P &lt; 0.001).

Conclusions
AD, in particular when severe, is associated with lower school performance in childhood and IQ in young men, which can interfere with academic achievements in life. Optimization of treatment of children with AD and specific educational support to children with severe AD could be needed.
Past climate changes and geographical barriers: the evolutionary history of a subtropical highland grassland species of Solanaceae,Petunia altiplana
Authors: Soares Luana S , Fagundes Nelson J R , Freitas Loreta B 
Published: January 2023

AbstractClimate changes and associated glacial and interglacial cycles during the Quaternary strongly influenced the evolutionary history of countless number of species. Subtropical highland grasslands (SHG) in southern South America constitute a distinct vegetation type with high diversity and endemism rates. The most recent common ancestor of the genus Petunia (Solanaceae) originated in lowland grasslands, and some lineages secondarily migrated to SHG. Here, we describe the evolutionary history of an SHG species, P. altiplana, distributed throughout a wide area in a river-fragmented landscape. We used plastid and nuclear markers to evaluate the role of the Pelotas River and Quaternary climate cycles over the genetic structure and historical demography of this species based on a phylogeographical approach. We found moderate population expansions during the last 25 kyr, with a more recent (c. 1.6 kya) divergence between two groups of populations from opposite river margins, possibly caused by the expansion of the Araucaria Forest along the river valley, effectively isolating distinct grassland patches.
Auditory stimulation and deep learning predict awakening from coma after cardiac arrest
Authors: Aellen Florence M , Alnes Sigurd L , Loosli Fabian , Rossetti Andrea O , Zubler Frédéric , De Lucia Marzia , Tzovara Athina 
Published: January 2023

AbstractAssessing the integrity of neural functions in coma after cardiac arrest remains an open challenge. Prognostication of coma outcome relies mainly on visual expert scoring of physiological signals, which is prone to subjectivity and leaves a considerable number of patients in a ‘grey zone’, with uncertain prognosis. Quantitative analysis of EEG responses to auditory stimuli can provide a window into neural functions in coma and information about patients’ chances of awakening. However, responses to standardized auditory stimulation are far from being used in a clinical routine due to heterogeneous and cumbersome protocols. Here, we hypothesize that convolutional neural networks can assist in extracting interpretable patterns of EEG responses to auditory stimuli during the first day of coma that are predictive of patients’ chances of awakening and survival at 3 months. We used convolutional neural networks (CNNs) to model single-trial EEG responses to auditory stimuli in the first day of coma, under standardized sedation and targeted temperature management, in a multicentre and multiprotocol patient cohort and predict outcome at 3 months. The use of CNNs resulted in a positive predictive power for predicting awakening of 0.83 ± 0.04 and 0.81 ± 0.06 and an area under the curve in predicting outcome of 0.69 ± 0.05 and 0.70 ± 0.05, for patients undergoing therapeutic hypothermia and normothermia, respectively. These results also persisted in a subset of patients that were in a clinical ‘grey zone’. The network’s confidence in predicting outcome was based on interpretable features: it strongly correlated to the neural synchrony and complexity of EEG responses and was modulated by independent clinical evaluations, such as the EEG reactivity, background burst-suppression or motor responses. Our results highlight the strong potential of interpretable deep learning algorithms in combination with auditory stimulation to improve prognostication of coma outcome.
Rehabilitation enhances epothilone-induced locomotor recovery after spinal cord injury
Authors: Griffin Jarred M , Hingorani Jai Prakash Sonia , Bockemühl Till , Benner Jessica M , Schaffran Barbara , Moreno-Manzano Victoria , Büschges Ansgar , Bradke Frank 
Published: January 2023

AbstractMicrotubule stabilization through epothilones is a promising preclinical therapy for functional recovery following spinal cord injury that stimulates axon regeneration, reduces growth-inhibitory molecule deposition and promotes functional improvements. Rehabilitation therapy is the only clinically validated approach to promote functional improvements following spinal cord injury. However, whether microtubule stabilization can augment the beneficial effects of rehabilitation therapy or act in concert with it to further promote repair remains unknown. Here, we investigated the pharmacokinetic, histological and functional efficacies of epothilone D, epothilone B and ixabepilone alone or in combination with rehabilitation following a moderate contusive spinal cord injury. Pharmacokinetic analysis revealed that ixabepilone only weakly crossed the blood–brain barrier and was subsequently excluded from further investigations. In contrast, epothilones B and D rapidly distributed to CNS compartments displaying similar profiles after either subcutaneous or intraperitoneal injections. Following injury and subcutaneous administration of epothilone B or D, rats were subjected to 7 weeks of sequential bipedal and quadrupedal training. For all outcome measures, epothilone B was efficacious compared with epothilone D. Specifically, epothilone B decreased fibrotic scaring which was associated with a retention of fibronectin localized to perivascular cells in sections distal to the lesion. This corresponded to a decreased number of cells present within the intralesional space, resulting in less axons within the lesion. Instead, epothilone B increased serotonergic fibre regeneration and vesicular glutamate transporter 1 expression caudal to the lesion, which was not affected by rehabilitation. Multiparametric behavioural analyses consisting of open-field locomotor scoring, horizontal ladder, catwalk gait analysis and hindlimb kinematics revealed that rehabilitation and epothilone B both improved several aspects of locomotion. Specifically, rehabilitation improved open-field locomotor and ladder scores, as well as improving the gait parameters of limb coupling, limb support, stride length and limb speed; epothilone B improved these same gait parameters but also hindlimb kinematic profiles. Functional improvements by epothilone B and rehabilitation acted complementarily on gait parameters leading to an enhanced recovery in the combination group. As a result, principal component analysis of gait showed the greatest improvement in the epothilone B plus rehabilitation group. Thus, these results support the combination of epothilone B with rehabilitation in a clinical setting.
Machine learning for prediction of all-cause mortality after transcatheter aortic valve implantation
Authors: Kwiecinski Jacek , Dabrowski Maciej , Nombela-Franco Luis , Grodecki Kajetan , Pieszko Konrad , Chmielak Zbigniew , Pylko Anna , Hennessey Breda , Kalinczuk Lukasz , Tirado-Conte Gabriela , Rymuza Bartosz , Kochman Janusz , Opolski Maksymilian P , Huczek Zenon , Dweck Marc R , Dey Damini , Jimenez-Quevedo Pilar , Slomka Piotr , Witkowski Adam 
Published: January 2023

Abstract

Aims
Prediction of adverse events in mid-term follow-up after transcatheter aortic valve implantation (TAVI) is challenging. We sought to develop and validate a machine learning model for prediction of 1-year all-cause mortality in patients who underwent TAVI and were discharged following the index procedure.

Methods and results
The model was developed on data of patients who underwent TAVI at a high-volume centre between January 2013 and March 2019. Machine learning by extreme gradient boosting was trained and tested with repeated 10-fold hold-out testing using 34 pre- and 25 peri-procedural clinical variables. External validation was performed on unseen data from two other independent high-volume TAVI centres. Six hundred four patients (43% men, 81 ± 5 years old, EuroSCORE II 4.8 [3.0–6.3]%) in the derivation and 823 patients (46% men, 82 ± 5 years old, EuroSCORE II 4.7 [2.9–6.0]%) in the validation cohort underwent TAVI and were discharged home following the index procedure. Over the 12 months of follow-up, 68 (11%) and 95 (12%) subjects died in the derivation and validation cohorts, respectively. In external validation, the machine learning model had an area under the receiver-operator curve of 0.82 (0.78–0.87) for prediction of 1-year all-cause mortality following hospital discharge after TAVI, which was superior to pre- and peri-procedural clinical variables including age 0.52 (0.46–0.59) and the EuroSCORE II 0.57 (0.51–0.64), P &lt; 0.001 for a difference.

Conclusion
Machine learning based on readily available clinical data allows accurate prediction of 1-year all-cause mortality following a successful TAVI.
Decoupling of height growth and drought or pest resistance tradeoffs is revealed through multiple common-garden experiments of lodgepole pine
Authors: Liu Yang , Erbilgin Nadir , Cappa Eduardo Pablo , Chen Charles , Ratcliffe Blaise , Wei Xiaojing , Klutsch Jennifer G , Ullah Aziz , Azcona Jaime Sebastian , Thomas Barb R , El-Kassaby Yousry A 
Published: January 2023

AbstractThe environment could alter growth and resistance tradeoffs in plants by affecting the ratio of resource allocation to various competing traits. Yet, how and why functional tradeoffs change over time and space is poorly understood particularly in long-lived conifer species. By establishing four common-garden test sites for five lodgepole pine populations in western Canada, combined with genomic sequencing, we revealed the decoupling pattern and genetic underpinnings of tradeoffs between height growth, drought resistance based on δ13C and dendrochronology, and metrics of pest resistance based on pest suitability ratings. Height and δ13C correlation displayed a gradient change in magnitude and/or direction along warm-to-cold test sites. All cold test sites across populations showed a positive height and δ13C relationship. However, we did not observe such a clinal correlation pattern between height or δ13C and pest suitability. Further, we found that the study populations exhibiting functional tradeoffs or synergies to various degrees in test sites were driven by non-adaptive evolutionary processes rather than adaptive evolution or plasticity. Finally, we found positive genetic relationships between height and drought or pest resistance metrics and probed five loci showing potential genetic tradeoffs between northernmost and the other populations. Our findings have implications for deciphering the ecological, evolutionary, and genetic bases of the decoupling of functional tradeoffs due to environmental change.
Can we ignore trait-dependent colonization and diversification in island biogeography?
Authors: Xie Shu , Valente Luis , Etienne Rampal S 
Published: January 2023

AbstractThe application of state-dependent speciation and extinction models to phylogenetic trees has shown an important role for traits in diversification. However, this role remains comparatively unexplored on islands, which can include multiple independent clades resulting from different colonization events. To explore whether assuming no dependence on traits leads to bias in inference on island dynamics, we extend an island biodiversity model, DAISIE (Dynamic Assembly of Islands through Speciation, Immigration, and Extinction) to include trait-dependent diversification simulations, and evaluate the robustness of the inference model which ignores this trait-dependence. Our results indicate that when the differences between colonization, extinction, and speciation rates between trait states are moderate, the model shows negligible error for a variety of island diversity metrics, suggesting that island diversity dynamics can be accurately estimated without the need to explicitly model trait dependence. We conclude that for many biologically realistic scenarios with trait-dependent diversification and colonization, this simple trait-less inference model is informative and robust to trait effects on colonization, speciation, and extinction. Nonetheless, our new simulation model may provide a useful tool for studying patterns of trait variation.
A forensic case of hydranencephaly in a preterm neonate fully documented by postmortem imaging techniques
Authors: Egger Coraline , Dédouit Fabrice , Schrag Bettina , Hanquinet Sylviane , Fracasso Tony 
Published: January 2023

Abstract

The authors present a medico-legal autopsy case of hydranencephaly in a male preterm newborn, fully documented by postmortem unenhanced and enhanced imaging techniques (postmortem computed tomography and postmortem magnetic resonance imaging). Hydranencephaly is a congenital anomaly of the central nervous system, consisting in almost complete absence of the cerebral hemispheres and replacement of the cerebral parenchyma by cerebrospinal fluid, rarely encountered in forensic medical practice. A premature baby was born during the supposed 22nd and 24th week of pregnancy in the context of a denial of pregnancy without any follow-up. The newborn died a few hours after birth and medico-legal investigations were requested to determine the cause of death and exclude the intervention of a third person in the lethal process. The external examination revealed neither traumatic nor malformative lesions. Postmortem imaging investigations were typical of hydranencephaly, and conventional medico-legal autopsy, neuropathological examination, and histological examination confirmed a massive necrotic-haemorrhagic hydranencephaly. This case represents in itself an association of out-of-the-ordinary elements making it worthy of interest.

Key Points
A combinatorial DNA assembly approach to biosynthesis ofN-linked glycans inE. coli
Authors: Passmore Ian J , Faulds-Pain Alexandra , Abouelhadid Sherif , Harrison Mark A , Hall Catherine L , Hitchen Paul , Dell Anne , Heap John T , Wren Brendan W 
Published: January 2023

AbstractGlycoengineering of recombinant glycans and glycoconjugates is a rapidly evolving field. However, the production and exploitation of glycans has lagged behind that of proteins and nucleic acids. Biosynthetic glycoconjugate production requires the coordinated cooperation of three key components within a bacterial cell: a substrate protein, a coupling oligosaccharyltransferase, and a glycan biosynthesis locus. While the acceptor protein and oligosaccharyltransferase are the products of single genes, the glycan is a product of a multigene metabolic pathway. Typically, the glycan biosynthesis locus is cloned and transferred en bloc from the native organism to a suitable Escherichia coli strain. However, gene expression within these pathways has been optimized by natural selection in the native host and is unlikely to be optimal for heterologous production in an unrelated organism. In recent years, synthetic biology has addressed the challenges in heterologous expression of multigene systems by deconstructing these pathways and rebuilding them from the bottom up. The use of DNA assembly methods allows the convenient assembly of such pathways by combining defined parts with the requisite coding sequences in a single step. In this study, we apply combinatorial assembly to the heterologous biosynthesis of the Campylobacter jejuni N-glycosylation (pgl) pathway in E. coli. We engineered reconstructed biosynthesis clusters that faithfully reproduced the C. jejuni heptasaccharide glycan. Furthermore, following a single round of combinatorial assembly and screening, we identified pathway clones that outperform glycan and glycoconjugate production of the native unmodified pgl cluster. This platform offers a flexible method for optimal engineering of glycan structures in E. coli.
Sustained Diet-Induced Remission in Pediatric Crohn’s Disease Is Associated With Kynurenine and Serotonin Pathways
Authors: Ghiboub Mohammed , Boneh Rotem Sigall , Sovran Bruno , Wine Eytan , Lefèvre Antoine , Emond Patrick , Verburgt Charlotte M , Benninga Marc A , de Jonge Wouter J , Van Limbergen Johan E 
Published: January 2023

Abstract

Background
Both the Crohn’s disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn’s disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission.

Methods
A total of 21 tryptophan metabolites were quantified in fecal samples from a 12-week prospective randomized trial with CDED+PEN or EEN for induction of remission in mild to moderate pediatric Crohn’s disease. Tryptophan metabolites at week 0 (W0), W6, and W12 of 73 samples were quantitatively measured by liquid chromatography coupled with triple quadrupole mass spectrometry, and data were analyzed according to clinical groups of baselines (W0), induced remission at W6, no remission, sustained remission at W12, and nonsustained remission.

Results
Reduction in components of the kynurenine pathway, such as kynurenine and quinolinic acid, were strongly associated with induced remission with both CDED+PEN and EEN, which were maintained in sustained remission. Specific serotonin pathway metabolites, such as melatonin, N-acetylserotonin, and 5-OH-tryptophan, were significantly increased in fecal samples from patients maintaining remission at W12 with both CDED+PEN and EEN. Importantly, in samples from patients failing to sustain remission, no changes were observed. Remission induction with EEN differs from CDED+PEN, particularly the moderate effects on indole pathway metabolites. The ratios of kynurenine and melatonin and quinolinic acid and melatonin perform well as markers for sustained remission.

Conclusions
The reduction in specific kynurenine pathway compounds and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. Further studies are warranted to assess causality and the association of these metabolites with specific diet and lifestyle factors, affecting sustained clinical remission.
Sovereign debt default and inequality
Authors: Apeti Ablam Estel 
Published: January 2023

AbstractBased on a sample of 124 developing countries over the period 1980–2016, we find that default increases inequality. This result, which passes a series of robustness tests, is sensitive to the size of the debt in default, the duration of the default episode, the institutional quality, the level of development, and the type of default (on external or domestic debt) and may persist until 5 years after the end of the default episode. Besides, the declines in redistributive capacity characterized by lower taxes and subsidies and social spending are identified as channels through which default increases inequality in default countries vis-à-vis nondefault countries. Finally, additional results show that default also raises wealth inequality.