bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/Cas9 genome editing of potato StDMR6-1 results in plants less affected by different stress conditions
Authors: Karlsson Milla , Kieu Nam Phuong , Lenman Marit , Marttila Salla , Resjö Svante , Zahid Muhammad Awais , Andreasson Erik 
Published: May 2024

Abstract
Potato is the third most important food crop, but cultivation is challenged by numerous diseases and adverse abiotic conditions. To combat diseases, frequent fungicide application is common. Knocking out susceptibility genes by genome editing could be a durable option to increase resistance. DMR6 has been described as a susceptibility gene in several crops, based on data that indicates increased resistance upon interruption of the gene function. In potato, Stdmr6-1 mutants have been described to have increased resistance against the late blight pathogen Phytophthora infestans in controlled conditions. Here, we present field evaluations of CRISPR/Cas9 mutants, in a location with a complex population of P. infestans, during four consecutive years that indicate increased resistance to late blight without any trade-off in terms of yield penalty or tuber quality. Furthermore, studies of potato tubers from the field trials indicated increased resistance to common scab, and the mutant lines exhibit increased resistance to early blight pathogen Alternaria solani in controlled conditions. Early blight and common scab are problematic targets in potato resistance breeding, as resistance genes are very scarce. The described broad-spectrum resistance of Stdmr6-1 mutants may further extend to some abiotic stress conditions. In controlled experiments of either drought simulation or salinity, Stdmr6-1 mutant plants are less affected than the background cultivar. Together, these results demonstrate the prospect of the Stdmr6-1 mutants as a useful tool in future sustainable potato cultivation without any apparent trade-offs.
Covariate shift in nonparametric regression with Markovian design
Authors: Trottner Lukas 
Published: May 2024

Abstract
Covariate shift in regression problems and the associated distribution mismatch between training and test data is a commonly encountered phenomenon in machine learning. In this paper, we extend recent results on nonparametric convergence rates for i.i.d. data to Markovian dependence structures. We demonstrate that under Hölder smoothness assumptions on the regression function, convergence rates for the generalization risk of a Nadaraya–Watson kernel estimator are determined by the similarity between the invariant distributions associated to source and target Markov chains. The similarity is explicitly captured in terms of a bandwidth-dependent similarity measure recently introduced in Pathak, Ma and Wainwright [ICML, 2022]. Precise convergence rates are derived for the particular cases of finite Markov chains and spectral gap Markov chains for which the similarity measure between their invariant distributions grows polynomially with decreasing bandwidth. For the latter, we extend the notion of a distribution transfer exponent from Kpotufe and Martinet [Ann. Stat., 49(6), 2021] to kernel transfer exponents of uniformly ergodic Markov chains in order to generate a rich class of Markov kernel pairs for which convergence guarantees for the covariate shift problem can be formulated.
The underestimated fraction: diversity, challenges and novel insights into unicellular cyanobionts of lichens
Authors: Jung Patrick , Briegel-Williams Laura , Büdel Burkhard , Schultz Matthias , Nürnberg Dennis J , Grube Martin , D’Agostino Paul M , Kaštovský Jan , Mareš Jan , Lorenz Maike , González Manuel Luis Gil , Forno Manuela Dal , Westberg Martin , Chrismas Nathan , Pietrasiak Nicole , Whelan Paul , Dvořák Petr , Košuthová Alica , Gkelis Spyros , Bauersachs Thorsten , Schiefelbein Ulf , Giao Võ Thị Phi , Lakatos Michael ,   INCb,   International Network for research on unicellular CyanoBionts from lichens
Published: May 2024

Abstract
Lichens are remarkable and classic examples of symbiotic organisms that have fascinated scientists for centuries. Yet, it has only been for a couple of decades that significant advances have focused on the diversity of their green algal and/or cyanobacterial photobionts. Cyanolichens, which contain cyanobacteria as their photosynthetic partner, include up to 10% of all known lichens and, as such, studies on their cyanobionts are much rarer compared to their green algal counterparts. For the unicellular cyanobionts, i.e. cyanobacteria that do not form filaments, these studies are even scarcer. Nonetheless, these currently include at least 10 different genera in the cosmopolitan lichen order Lichinales. An international consortium (International Network of CyanoBionts; INCb) will tackle this lack of knowledge. In this article, we discuss the status of current unicellular cyanobiont research, compare the taxonomic resolution of photobionts from cyanolichens with those of green algal lichens (chlorolichens), and give a roadmap of research on how to recondition the underestimated fraction of symbiotic unicellular cyanobacteria in lichens.
Use of the FebriDx® host-response point-of-care test may reduce antibiotic use for respiratory tract infections in primary care: a mixed-methods feasibility study
Authors: Wilcox Christopher R , Odeh Nour , Clark Tristan W , Muller Ingrid , Becque Taeko , Todd Alexander , Islam Nazrul , Little Paul , Davies Firoza , McGavin John , Francis Nick 
Published: May 2024

Abstract

Introduction
FebriDx® is a CE-marked, single-use point-of-care test with markers for bacterial [C-reactive protein (CRP)] and viral [myxovirus resistance protein A (MxA)] infection, using finger-prick blood samples. Results are available after 10–12 min. We explored the usability and potential impact of FebriDx® in reducing antibiotic prescriptions for lower respiratory tract infection (LRTI) in primary care, and the feasibility of conducting a randomized controlled trial (RCT).

Methods
Patients (aged ≥1 year) with LRTI deemed likely to receive antibiotic prescription were recruited at nine general practices and underwent FebriDx® testing. Data collection included FebriDx® results, antibiotic prescribing plan (before and after testing) and re-consultation rates. Staff completed System Usability Scale questionnaires.

Results
From 31 January 2023 to 9 June 2023, 162 participants participated (median age 57 years), with a median symptom duration of 7 days (IQR 5–14). A valid FebriDx® result was obtained in 97% (157/162). Of 155 patients with available results, 103 (66%) had no detectable CRP or MxA, 28 (18%) had CRP only, 5 (3%) had MxA only, and 19 (12%) had both CRP and MxA. The clinicians’ stated management plan was to prescribe antibiotics for 86% (134/155) before testing and 45% (69/155) after testing, meaning a 41% (95% CI: 31%, 51%) difference after testing, without evidence of increased re-consultation rates. Ease-of-use questionnaires showed ‘good’ user-friendliness.

Conclusions
Use of FebriDx® to guide antibiotic prescribing for LRTI in primary care was associated with a substantial reduction in prescribing intentions. These results support a fully powered RCT to confirm its impact and safety.
RT: a Retrieving and Chain-of-Thought framework for few-shot medical named entity recognition
Authors: Li Mingchen , Zhou Huixue , Yang Han , Zhang Rui 
Published: May 2024

Abstract

Objectives
This article aims to enhance the performance of larger language models (LLMs) on the few-shot biomedical named entity recognition (NER) task by developing a simple and effective method called Retrieving and Chain-of-Thought (RT) framework and to evaluate the improvement after applying RT framework.

Materials and Methods
Given the remarkable advancements in retrieval-based language model and Chain-of-Thought across various natural language processing tasks, we propose a pioneering RT framework designed to amalgamate both approaches. The RT approach encompasses dedicated modules for information retrieval and Chain-of-Thought processes. In the retrieval module, RT discerns pertinent examples from demonstrations during instructional tuning for each input sentence. Subsequently, the Chain-of-Thought module employs a systematic reasoning process to identify entities. We conducted a comprehensive comparative analysis of our RT framework against 16 other models for few-shot NER tasks on BC5CDR and NCBI corpora. Additionally, we explored the impacts of negative samples, output formats, and missing data on performance.

Results
Our proposed RT framework outperforms other LMs for few-shot NER tasks with micro-F1 scores of 93.50 and 91.76 on BC5CDR and NCBI corpora, respectively. We found that using both positive and negative samples, Chain-of-Thought (vs Tree-of-Thought) performed better. Additionally, utilization of a partially annotated dataset has a marginal effect of the model performance.

Discussion
This is the first investigation to combine a retrieval-based LLM and Chain-of-Thought methodology to enhance the performance in biomedical few-shot NER. The retrieval-based LLM aids in retrieving the most relevant examples of the input sentence, offering crucial knowledge to predict the entity in the sentence. We also conducted a meticulous examination of our methodology, incorporating an ablation study.

Conclusion
The RT framework with LLM has demonstrated state-of-the-art performance on few-shot NER tasks.
What We Argue About When We Argue About Death
Authors: Aas Sean 
Published: May 2024

Abstract
The literature on the determination of death has often if not always assumed that the concept of human death should be defined in terms of the end of the human organism. I argue that this broadly biological conceptualization of human death cannot constitute a basis for agreement in a pluralistic society characterized by a variety of reasonable views on the nature of our existence as embodied beings. Rather, following Robert Veatch, I suggest that we must define death in moralized terms, as the loss of an especially significant sort of moral standing. Departing from Veatch, however, I argue that we should not understand death in terms of the loss of all moral status whatsoever. Rather, I argue, what we should argue about, when we argue about death, is when and why people lose their rights-claims to the protection and promotion of their basic bodily functioning.
Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis
Authors: Song Zeyu , Li Zhenyuan , Pan Tao , Liu Teng , Gong Baifang , Wang Zhixia , Liu Ke , Fan Huaying 
Published: May 2024

Abstract

Objectives
Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms.

Methods
In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins.

Results
PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system.

Conclusion
PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.
Estimating disease transmission in a closed population under repeated testing
Authors: Wascher Matthew , Schnell Patrick M , KhudaBukhsh Wasiur R , Quam Mikkel B M , Tien Joesph H , Rempała Grzegorz A 
Published: May 2024

Abstract
The article presents a novel statistical framework for COVID-19 transmission monitoring and control, which was developed and deployed at The Ohio State University main campus in Columbus during the Autumn term of 2020. Our approach effectively handles prevalence data with interval censoring and explicitly incorporates changes in transmission dynamics and human behaviour. To illustrate the methodology’s usefulness, we apply it to both synthetic and actual student SARS-CoV-2 testing data collected at the OSU Columbus campus in late 2020.
Unpredictability of the Fitness Effects of Antimicrobial Resistance Mutations Across Environments in Escherichia coli
Authors: Hinz Aaron , Amado André , Kassen Rees , Bank Claudia , Wong Alex 
Published: May 2024

Abstract
The evolution of antimicrobial resistance (AMR) in bacteria is a major public health concern, and antibiotic restriction is often implemented to reduce the spread of resistance. These measures rely on the existence of deleterious fitness effects (i.e. costs) imposed by AMR mutations during growth in the absence of antibiotics. According to this assumption, resistant strains will be outcompeted by susceptible strains that do not pay the cost during the period of restriction. The fitness effects of AMR mutations are generally studied in laboratory reference strains grown in standard growth environments; however, the genetic and environmental context can influence the magnitude and direction of a mutation's fitness effects. In this study, we measure how three sources of variation impact the fitness effects of Escherichia coli AMR mutations: the type of resistance mutation, the genetic background of the host, and the growth environment. We demonstrate that while AMR mutations are generally costly in antibiotic-free environments, their fitness effects vary widely and depend on complex interactions between the mutation, genetic background, and environment. We test the ability of the Rough Mount Fuji fitness landscape model to reproduce the empirical data in simulation. We identify model parameters that reasonably capture the variation in fitness effects due to genetic variation. However, the model fails to accommodate the observed variation when considering multiple growth environments. Overall, this study reveals a wealth of variation in the fitness effects of resistance mutations owing to genetic background and environmental conditions, which will ultimately impact their persistence in natural populations.
mtDNA-Server 2: advancing mitochondrial DNA analysis through highly parallelized data processing and interactive analytics
Authors: Weissensteiner Hansi , Forer Lukas , Kronenberg Florian , Schönherr Sebastian 
Published: May 2024

Abstract
Over the past decade, mtDNA-Server established itself as one of the most widely used variant calling web-services for human mitochondrial genomes. The service accepts sequencing data in BAM format and returns an annotated variant analysis report for both homoplasmic and heteroplasmic variants. In this work we present mtDNA-Server 2, which includes several new features highly requested by the community. Most importantly, it includes (a) the integration of a novel variant calling mode that accurately call insertions, deletions and single nucleotide variants at once, (b) the integration of additional quality control and input validation modules, (c) a method to estimate the required coverage to minimize false positives and (d) an interactive analytics dashboard. Furthermore, we migrated the complete analysis workflow to the Nextflow workflow manager for improved parallelization, reproducibility and local execution. Recognizing the importance of insertions and deletions as well as offering novel quality control, validation and reporting features, mtDNA-Server 2 provides researchers and clinicians a new state-of-the-art analysis platform for interpreting mitochondrial genomes. mtDNA-Server 2 is available via mitoverse, our analysis platform that offers a centralized place for mtDNA analysis in the cloud. The web-service, source code and its documentation are freely accessible at https://mitoverse.i-med.ac.at.
UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2
Authors: Langer Lukas M , Kurscheidt Katharina , Basquin Jérôme , Bonneau Fabien , Iermak Iuliia , Basquin Claire , Conti Elena 
Published: May 2024

Abstract
Nonsense-mediated mRNA decay (NMD) is a conserved co-translational mRNA surveillance and turnover pathway across eukaryotes. NMD has a central role in degrading defective mRNAs and also regulates the stability of a significant portion of the transcriptome. The pathway is organized around UPF1, an RNA helicase that can interact with several NMD-specific factors. In human cells, degradation of the targeted mRNAs begins with a cleavage event that requires the recruitment of the SMG6 endonuclease to UPF1. Previous studies have identified functional links between SMG6 and UPF1, but the underlying molecular mechanisms have remained elusive. Here, we used mass spectrometry, structural biology and biochemical approaches to identify and characterize a conserved short linear motif in SMG6 that interacts with the cysteine/histidine-rich (CH) domain of UPF1. Unexpectedly, we found that the UPF1–SMG6 interaction is precluded when the UPF1 CH domain is engaged with another NMD factor, UPF2. Based on cryo-EM data, we propose that the formation of distinct SMG6-containing and UPF2-containing NMD complexes may be dictated by different conformational states connected to the RNA-binding status of UPF1. Our findings rationalize a key event in metazoan NMD and advance our understanding of mechanisms regulating activity and guiding substrate recognition by the SMG6 endonuclease.
GPS-SUMO 2.0: an updated online service for the prediction of SUMOylation sites and SUMO-interacting motifs
Authors: Gou Yujie , Liu Dan , Chen Miaomiao , Wei Yuxiang , Huang Xinhe , Han Cheng , Feng Zihao , Zhang Chi , Lu Teng , Peng Di , Xue Yu 
Published: May 2024

Abstract
Small ubiquitin-like modifiers (SUMOs) are tiny but important protein regulators involved in orchestrating a broad spectrum of biological processes, either by covalently modifying protein substrates or by noncovalently interacting with other proteins. Here, we report an updated server, GPS-SUMO 2.0, for the prediction of SUMOylation sites and SUMO-interacting motifs (SIMs). For predictor training, we adopted three machine learning algorithms, penalized logistic regression (PLR), a deep neural network (DNN), and a transformer, and used 52 404 nonredundant SUMOylation sites in 8262 proteins and 163 SIMs in 102 proteins. To further increase the accuracy of predicting SUMOylation sites, a pretraining model was first constructed using 145 545 protein lysine modification sites, followed by transfer learning to fine-tune the model. GPS-SUMO 2.0 exhibited greater accuracy in predicting SUMOylation sites than did other existing tools. For users, one or multiple protein sequences or identifiers can be input, and the prediction results are shown in a tabular list. In addition to the basic statistics, we integrated knowledge from 35 public resources to annotate SUMOylation sites or SIMs. The GPS-SUMO 2.0 server is freely available at https://sumo.biocuckoo.cn/. We believe that GPS-SUMO 2.0 can serve as a useful tool for further analysis of SUMOylation and SUMO interactions.
SHAPEwarp-web: sequence-agnostic search for structurally homologous RNA regions across databases of chemical probing data
Authors: Scholten Niek R , Haandrikman Dennis , Tolhuis Joshua O , Morandi Edoardo , Incarnato Danny 
Published: May 2024

Abstract
RNA molecules perform a variety of functions in cells, many of which rely on their secondary and tertiary structures. Chemical probing methods coupled with high-throughput sequencing have significantly accelerated the mapping of RNA structures, and increasingly large datasets of transcriptome-wide RNA chemical probing data are becoming available. Analogously to what has been done for decades in the protein world, this RNA structural information can be leveraged to aid the discovery of structural similarity to a known RNA (or RNA family), which, in turn, can inform about the function of transcripts. We have previously developed SHAPEwarp, a sequence-agnostic method for the search of structurally homologous RNA segments in a database of reactivity profiles derived from chemical probing experiments. In its original implementation, however, SHAPEwarp required substantial computational resources, even for moderately sized databases, as well as significant Linux command line know-how. To address these limitations, we introduce here SHAPEwarp-web, a user-friendly web interface to rapidly query large databases of RNA chemical probing data for structurally similar RNAs. Aside from featuring a completely rewritten core, which speeds up by orders of magnitude the search inside large databases, the web server hosts several high-quality chemical probing databases across multiple species. SHAPEwarp-web is available from https://shapewarp.incarnatolab.com.
Analysis of swimming trajectories in Daphnia similis as an environmental impact assessment tool
Authors: Lopes Rubens M , Akari Marcia , De La Cruz Leandro T , Uttieri Marco 
Published: May 2024

Abstract
Toxicity tests with daphnids are important tools in the environmental impact assessment of aquatic ecosystems. The aim of this study was to characterize the swimming paths of Daphnia similis in response to two concentrations of the reference substance potassium chloride (KCl), as an additional expedite tool in evaluating the effects of contaminants. Bidimensional trajectory coordinates were obtained with image acquisition and processing methods and used to calculate the following metrics of D. similis behavior: mean swimming speed, hop rate, fractal dimension, and vertical occupancy. The swimming speed, hop rate and fractal dimension for the control group were significantly different from the KCl treatment at the higher concentration. Conversely, the vertical occupancy did not differ between the experimental conditions. The results of this investigation validate the use of behavioral analysis as a rapid and reliable approach to evaluate water contamination, aiding in early warning detection of water quality issues. The method can be further refined through the integration of machine learning applications in video tracking.
What ‘case definition’ for respiratory syncytial virus infection? Results of a systematic literature review to improve surveillance among the adults
Authors: Amodio Emanuele , Belluzzo Miriam , Genovese Dario , Palermo Martina , Pisciotta Vincenzo , Vitale Francesco 
Published: May 2024

Abstract

Background
Human respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in frail individuals, including children, the elderly and immunocompromised people, with mild to severe symptoms. World Health Organization claims hRSV causes most elderly influenza-like illnesses (ILI) and severe acute respiratory infections (SARI). In this study, different case definitions for hRSV surveillance were examined for accuracy.

Methods
The following search query (‘Respiratory Syncytial Virus’ OR ‘RSV’ OR ‘hRSV’ AND ‘case definition’) was used on PubMed/MEDLINE and Scopus with a 15-year-old baseline age restriction to conduct a systematic literature review.

Results
Of 12 records, 58% employed the SARI definition, 50% the ILI definition and 42% the acute respiratory infection (ARI) definition, with some overlap. In young adults (18–64 years old), most studies show RSV prevalence between 6.25 and 72.54 cases per 1000 per year, and 19.23 to 98.5 in older adults. The outpatient ARI and hospitalized SARI criteria are particularly sensitive and specific.

Conclusions
Disease burden measurement requires a clear case definition; however, current literature is questionable. Currently, hRSV surveillance uses numerous case definitions with debatable accuracy. The epidemiology, clinical characteristics, and disease burden of hRSV are difficult to characterize without a standard surveillance case definition.