bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and risk of herpes zoster in patients with ulcerative colitis and Crohn’s disease in the USA
Authors: Singer David , Thompson-Leduc Philippe , Gupta Deepshekhar , Cheng Wendy Y , Poston Sara , Ma Siyu , Pawlowski John E , Duh Mei Sheng , Morris Eric D , Devine Francesca , Farraye Francis A 
Published: April 2023

AbstractBackgroundPatients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ). We evaluated the incidence of HZ in ulcerative colitis (UC) and Crohn’s disease (CD) patients and compared this with HZ incidence in a non-IBD population.MethodsWe conducted a retrospective cohort study (GSK study identifier: VEO-000043) of adults aged ≥18 years with UC and CD and without IBD who were identified from claims recorded in a US healthcare database between October 2015 and February 2020. Crude HZ incidence rates/1,000 person-years (PY) were calculated, and comparisons of HZ incidence rates between UC or CD and non-IBD cohorts were made using adjusted generalized linear models.ResultsThe study population comprised a total of 29,928 UC, 25,959 CD, and 11,839,329 non-IBD patients. Crude overall HZ incidence rates were 13.64/1,000 PY (UC), 15.94/1,000 PY (CD), and 7.95/1,000 PY (non-IBD). UC and CD patients had increased HZ incidence rates, with adjusted incidence rate ratios of 1.35 (95% confidence interval [CI], 1.26–1.44) and 1.66 (95% CI, 1.56–1.77), respectively, compared with non-IBD patients. Stratified analysis indicated increased relative rates of HZ in progressively younger age strata in the UC and CD patients compared with non-IBD patients. HZ incidence rates were higher in UC and CD patients who had previously received thiopurines or methotrexate, TNF-inhibitors, or corticosteroids than in UC and CD patients who did not take those medicines.ConclusionUC and CD patients had increased HZ incidence rates compared with patients without IBD, demonstrating the importance of HZ prevention in IBD patients.
Modeling the Impact of a Highly Potent Plasmodium falciparum Transmission-Blocking Monoclonal Antibody in Areas of Seasonal Malaria Transmission
Authors: Challenger Joseph D , van Beek Stijn W , ter Heine Rob , van der Boor Saskia C , Charles Giovanni D , Smit Merel J , Ockenhouse Chris , Aponte John J , McCall Matthew B B , Jore Matthijs M , Churcher Thomas S , Bousema Teun 
Published: April 2023

Abstract
Transmission-blocking interventions can play an important role in combating malaria worldwide. Recently, a highly potent Plasmodium falciparum transmission-blocking monoclonal antibody (TB31F) was demonstrated to be safe and efficacious in malaria-naive volunteers. Here we predict the potential public health impact of large-scale implementation of TB31F alongside existing interventions. We developed a pharmaco-epidemiological model, tailored to 2 settings of differing transmission intensity with already established insecticide-treated nets and seasonal malaria chemoprevention interventions. Community-wide annual administration (at 80% coverage) of TB31F over a 3-year period was predicted to reduce clinical incidence by 54% (381 cases averted per 1000 people per year) in a high-transmission seasonal setting, and 74% (157 cases averted per 1000 people per year) in a low-transmission seasonal setting. Targeting school-aged children gave the largest reduction in terms of cases averted per dose. An annual administration of the transmission-blocking monoclonal antibody TB31F may be an effective intervention against malaria in seasonal malaria settings.
Predicting risk of metastases and recurrence in soft-tissue sarcomas via Radiomics and Formal Methods
Authors: Casale Roberto , Varriano Giulia , Santone Antonella , Messina Carmelo , Casale Chiara , Gitto Salvatore , Sconfienza Luca Maria , Bali Maria Antonietta , Brunese Luca 
Published: April 2023

Abstract

Objective
Soft-tissue sarcomas (STSs) of the extremities are a group of malignancies arising from the mesenchymal cells that may develop distant metastases or local recurrence. In this article, we propose a novel methodology aimed to predict metastases and recurrence risk in patients with these malignancies by evaluating magnetic resonance radiomic features that will be formally verified through formal logic models.

Materials and Methods
This is a retrospective study based on a public dataset evaluating MRI scans T2-weighted fat-saturated or short tau inversion recovery and patients having “metastases/local recurrence” (group B) or “no metastases/no local recurrence” (group A) as clinical outcomes. Once radiomic features are extracted, they are included in formal models, on which is automatically verified the logic property written by a radiologist and his computer scientists coworkers.

Results
Evaluating the Formal Methods efficacy in predicting distant metastases/local recurrence in STSs (group A vs group B), our methodology showed a sensitivity and specificity of 0.81 and 0.67, respectively; this suggests that radiomics and formal verification may be useful in predicting future metastases or local recurrence development in soft tissue sarcoma.

Discussion
Authors discussed about the literature to consider Formal Methods as a valid alternative to other Artificial Intelligence techniques.

Conclusions
An innovative and noninvasive rigourous methodology can be significant in predicting local recurrence and metastases development in STSs. Future works can be the assessment on multicentric studies to extract objective disease information, enriching the connection between the radiomic quantitative analysis and the radiological clinical evidences.
A matter of time: auxin signaling dynamics and the regulation of auxin responses during plant development
Authors: Caumon Hugo , Vernoux Teva 
Published: April 2023

Abstract
As auxin is a major regulator of plant development, studying the signaling mechanisms by which auxin influences cellular activities is of primary importance. In this review, we describe current knowledge on the different modalities of signaling, from the well-characterized canonical nuclear auxin pathway, to the more recently discovered or re-discovered non-canonical modes of auxin signaling. In particular, we discuss how both the modularity of the nuclear auxin pathway and the dynamic regulation of its core components allow specific transcriptomic responses to be triggered. We highlight the fact that the diversity of modes of auxin signaling allows for a wide range of time scales of auxin responses, from second-scale cytoplasmic responses to minute-/hour-scale modifications of gene expression. Finally, we question the extent to which the temporality of auxin signaling and responses contributes to development in both the shoot and the root meristems. We conclude by stressing the fact that future investigations should allow an integrative view to be built not only of the spatial control, but also of the temporality of auxin-mediated regulation of plant development, from the cell to the whole organism.
Automatic sentence segmentation for classical Chinese: The Spring and Autumn Annals as an example
Authors: Fan Wenjie , Wang Dongbo , Huang Shuiqing 
Published: April 2023

Abstract
There exists no sentence boundary in most classical Chinese literature texts. Since it is difficult to read literature of this kind, experts in literature or linguistics would segment the sentence manually. This article explores the effectiveness of classical Chinese sentence segmentation method so as to provide a reference for classical Chinese punctuation. On the basis of the machine learning methods, we chose three components of machine learning, namely models, tagging schemes, and features, to compare the learning results. The models include conditional random field (CRF) models, long short term memory (LSTM) models, BiLSTM–CRF models, and three Bidirectional Encoder Representation from Transformers (BERT) models. There are five tagging schemes in this article and three features including the statistical feature, Guangyun, and Fanqie. Finally, the performance of the combined feature template is evaluated by ten-fold cross-validation on four classical Chinese texts in different genres. The SikuBERT model is proved to be the most effective model for sentence segmentation at present. Different tagging schemes and various features are introduced. The results show that 5-tag-J tagging schemes can improve performance. Statistical feature, as an important clue for classical Chinese sentence segmentation, is useful in related tasks, but Guangyun and Fanqie have little impact. Other important factors of sentence segmentation are genres and writing styles.
Multiwavelength observations of the extraordinary accretion event AT2021lwx
Authors: Wiseman P , Wang Y , Hönig S , Castro-Segura N , Clark P , Frohmaier C , Fulton M D , Leloudas G , Middleton M , Müller-Bravo T E , Mummery A , Pursiainen M , Smartt S J , Smith K , Sullivan M , Anderson J P , Acosta Pulido J A , Charalampopoulos P , Banerji M , Dennefeld M , Galbany L , Gromadzki M , Gutiérrez C P , Ihanec N , Kankare E , Lawrence A , Mockler B , Moore T , Nicholl M , Onori F , Petrushevska T , Ragosta F , Rest S , Smith M , Wevers T , Carini R , Chen T-W , Chambers K , Gao H , Huber M , Inserra C , Magnier E , Makrygianni L , Toy M , Vincentelli F , Young D R 
Published: April 2023

ABSTRACT
We present observations from X-ray to mid-infrared wavelengths of the most energetic non-quasar transient ever observed, AT2021lwx. Our data show a single optical brightening by a factor &gt;100 to a luminosity of 7 × 1045 erg s−1 and a total radiated energy of 1.5 × 1053 erg, both greater than any known optical transient. The decline is smooth and exponential and the ultraviolet–optical spectral energy distribution resembles a blackbody with a temperature of 1.2 × 104 K. Tentative X-ray detections indicate a secondary mode of emission, while a delayed mid-infrared flare points to the presence of dust surrounding the transient. The spectra are similar to recently discovered optical flares in known active galactic nuclei but lack some characteristic features. The lack of emission for the previous 7 yr is inconsistent with the short-term, stochastic variability observed in quasars, while the extreme luminosity and long time-scale of the transient disfavour the disruption of a single solar-mass star. The luminosity could be generated by the disruption of a much more massive star, but the likelihood of such an event occurring is small. A plausible scenario is the accretion of a giant molecular cloud by a dormant black hole of 108–109 solar masses. AT2021lwx thus represents an extreme extension of the known scenarios of black hole accretion.
Pediatric diffuse midline glioma: Understanding the mechanisms and assessing the next generation of personalized therapeutics
Authors: Jovanovich Nicolina , Habib Ahmed , Head Jeffery , Hameed Farrukh , Agnihotri Sameer , Zinn Pascal O 
Published: April 2023

Abstract
Diffuse midline glioma (DMG) is a pediatric cancer that originates in the midline structures of the brain. Prognosis of DMG patients remains poor due to the infiltrative nature of these tumors and the protection they receive from systemically delivered therapeutics via an intact blood–brain barrier (BBB), making treatment difficult. While the cell of origin remains disputed, it is believed to reside in the ventral pons. Recent research has pointed toward epigenetic dysregulation inducing an OPC-like transcriptomic signature in DMG cells. This epigenetic dysregulation is typically caused by a mutation (K27M) in one of two histone genes—H3F3A or HIST1H3B –and can lead to a differentiation block that increases these cells oncogenic potential. Standard treatment with radiation is not sufficient at overcoming the aggressivity of this cancer and only confers a survival benefit of a few months, and thus, discovery of new therapeutics is of utmost importance. In this review, we discuss the cell of origin of DMGs, as well as the underlying molecular mechanisms that contribute to their aggressivity and resistance to treatment. Additionally, we outline the current standard of care for DMG patients and the potential future therapeutics for this cancer that are currently being tested in preclinical and clinical trials.
Principles and Terminology for Host–Microbiome–Drug Interactions
Authors: Heirali Alya , Moossavi Shirin , Arrieta Marie Claire , Coburn Bryan 
Published: April 2023

Abstract
Interactions between the microbiome and medical therapies are distinct and bidirectional. The existing term “pharmacomicrobiomics” describes the effects of the microbiome on drug distribution, metabolism, efficacy, and toxicity. We propose that the term “pharmacoecology” be used to describe the effects that drugs and other medical interventions such as probiotics have on microbiome composition and function. We suggest that the terms are complementary but distinct and that both are potentially important when assessing drug safety and efficacy as well as drug–microbiome interactions. As a proof of principle, we describe the ways in which these concepts apply to antimicrobial and non-antimicrobial medications.
Volatiles and Intraplate Magmatism: a Variable Role for Carbonated and Altered Oceanic Lithosphere in Ocean Island Basalt Formation
Authors: Kirstein Linda A , Walowski Kristina J , Jones Rosemary E , Burgess Ray , Fitton J Godfrey , De Hoog Jan C M , Savov Ivan P , Kalnins Lara M ,   E I M F
Published: April 2023

Abstract
Recycling of material at subduction zones has fundamental implications for melt composition and mantle rheology. Ocean island basalts (OIBs) sample parts of the mantle from variable depths that have been diversely affected by subduction zone processes and materials, including the subducted slab, metasomatising melts and fluids. Resultant geochemical differences are preserved at a variety of scales from melt inclusions to whole rocks, from individual islands to chains of islands. Here we examine a global dataset of ocean island basalt compositions with a view to understanding the connection between silica-saturation, olivine compositions, and halogens in glass and olivine-hosted melt inclusions to reveal information regarding the mantle sources of intraplate magmatism. We find that minor elements incorporated into olivine, although informative, cannot unambiguously discriminate between different source contributions, but indicate that none of the OIB analysed here are derived solely from dry peridotite melting. Nor can differences in lithospheric thickness explain trace element variability in olivine between different ocean islands. We present new halogen (F, Cl, Br/Cl, I/Cl) data along with incompatible trace element data for the global array and encourage measurement of fluorine along with heavier halogens to obtain better insight into halogen cycling. We suggest that Ti-rich silica-undersaturated melts require a contribution from carbonated lithosphere, either peridotite or eclogite and are an important component sampled by ocean island basalts, together with altered oceanic crust. These results provide new insights into our understanding of mantle-scale geochemical cycles, and also lead to the potential for the mantle transition zone as an underestimated source for observed volatile and trace-element enrichment in ocean island basalts.
The production of within-family inequality: Insights and implications of integrating genetic data
Authors: Fletcher Jason M , Wu Yuchang , Zhao Zijie , Lu Qiongshi 
Published: April 2023

Abstract
The integration of genetic data within large-scale social and health surveys provides new opportunities to test long-standing theories of parental investments in children and within-family inequality. Genetic predictors, called polygenic scores, allow novel assessments of young children's abilities that are uncontaminated by parental investments, and family-based samples allow indirect tests of whether children's abilities are reinforced or compensated. We use over 16,000 sibling pairs from the UK Biobank to test whether the relative ranking of siblings’ polygenic scores for educational attainment is consequential for actual attainments. We find evidence consistent with compensatory processes, on average, where the association between genotype and phenotype of educational attainment is reduced by over 20% for the higher-ranked sibling compared to the lower-ranked sibling. These effects are most pronounced in high socioeconomic status areas. We find no evidence that similar processes hold in the case of height or for relatives who are not full biological siblings (e.g. cousins). Our results provide a new use of polygenic scores to understand processes that generate within-family inequalities and also suggest important caveats to causal interpretations the effects of polygenic scores using sibling difference designs. Future work should seek to replicate these findings in other data and contexts.
Targeting thiol isomerase activity with zafirlukast to treat ovarian cancer from the bench to clinic
Authors: Gelzinis Justine A. , Szahaj Melanie K. , Bekendam Roelof H. , Wurl Sienna E. , Pantos Megan M. , Verbetsky Christina A. , Dufresne Alexandre , Shea Meghan , Howard Kaitlind C. , Tsodikov Oleg V. , Garneau‐Tsodikova Sylvie , Zwicker Jeffrey I. , Kennedy Daniel R. 
Published: April 2023

AbstractThiol isomerases, including PDI, ERp57, ERp5, and ERp72, play important and distinct roles in cancer progression, cancer cell signaling, and metastasis. We recently discovered that zafirlukast, an FDA‐approved medication for asthma, is a pan‐thiol isomerase inhibitor. Zafirlukast inhibited the growth of multiple cancer cell lines with an IC50 in the low micromolar range, while also inhibiting cellular thiol isomerase activity, EGFR activation, and downstream phosphorylation of Gab1. Zafirlukast also blocked the procoagulant activity of OVCAR8 cells by inhibiting tissue factor‐dependent Factor Xa generation. In an ovarian cancer xenograft model, statistically significant differences in tumor size between control vs treated groups were observed by Day 18. Zafirlukast also significantly reduced the number and size of metastatic tumors found within the lungs of the mock‐treated controls. When added to a chemotherapeutic regimen, zafirlukast significantly reduced growth, by 38% compared with the mice receiving only the chemotherapeutic treatment, and by 83% over untreated controls. Finally, we conducted a pilot clinical trial in women with tumor marker‐only (CA‐125) relapsed ovarian cancer, where the rate of rise of CA‐125 was significantly reduced following treatment with zafirlukast, while no severe adverse events were reported. Thiol isomerase inhibition with zafirlukast represents a novel, well‐tolerated therapeutic in the treatment of ovarian cancer.
RoMIA: A Framework for Creating Robust Medical Imaging AI
Authors: Anand Aditi , Krithivasan Sarada , Roy Kaushik 
Published: April 2023

AbstractArtificial Intelligence (AI) methods, particularly Artificial Neural Networks (ANNs) have shown great promise in a range of medical imaging tasks. Despite their promise, the susceptibility of ANNs to produce erroneous outputs under the presence of input noise, variations, or adversarial attacks is of great concern and one of the largest challenges to adoption in medical settings. Towards addressing this challenge, we explore the robustness of ANNs trained for chest radiograph classification under a range of perturbations reflective of clinical settings. We propose RoMIA, a framework for the creation ofRobustMedical ImagingANNs. RoMIA adds three key steps to the model training and deployment flow: (i) Noise-added training, wherein a part of the training data is synthetically transformed to represent common noise sources, (ii) Fine-tuning with input mixing, in which the model is refined with inputs formed by mixing data from the original training set with a small number of images from a different source, and (iii) DCT-based denoising, which removes a fraction of high-frequency components of each image before applying the model to classify it. We applied RoMIA to create six different robust ANNs for classifying chest radiographs using the CheXpert dataset. We evaluated the models on the CheXphoto dataset, consisting of naturally and synthetically perturbed images intended to evaluate robustness. Models produced by RoMIA show 3-5% improvement in robust accuracy, suggesting that the proposed methods can be a useful step towards enabling the adoption of ANNs in medical imaging applications.
Reducing the Mitochondrial Oxidative Burden Alleviates Lipid-Induced Muscle Insulin Resistance in Humans
Authors: Fiorenza Matteo , Onslev Johan , Henríquez-Olguín Carlos , Persson Kaspar W. , Hesselager Sofie A. , Jensen Thomas E. , Wojtaszewski Jørgen F.P. , Hostrup Morten , Bangsbo Jens 
Published: April 2023

ABSTRACTPre-clinical models suggest a causative nexus between mitochondrial oxidative stress and insulin resistance. However, the translational and pathophysiological significance of this mechanism in humans remains unclear. Herein, we employed an invasivein vivomechanistic approach in humans to manipulate mitochondrial redox state while assessing insulin action. To this end, we combined intravenous infusion of a lipid overload with intake of a mitochondria-targeted antioxidant (mtAO) in conjunction with insulin clamp studies. During lipid overload, insulin-stimulated muscle glucose uptake, as determined by the femoral arteriovenous balance technique, was increased by mtAO. At the muscle molecular level, mtAO did not affect canonical insulin signaling but augmented insulin-stimulated GLUT4 translocation while decreasing the mitochondrial oxidative burden under lipid oversupply.Ex vivostudies revealed that mtAO ameliorated features of mitochondrial bioenergetics, including diminished mitochondrial H2O2emission, in muscle fibers exposed to high intracellular lipid levels. These findings provide translational and mechanistic evidence implicating mitochondrial oxidants in the development of lipid-induced muscle insulin resistance in humans.GRAPHICAL ABSTRACT
ATP synthase evolution on a cross-braced dated tree of life
Authors: Mahendrarajah Tara A. , Moody Edmund R. R. , Schrempf Dominik , Szánthó Lénárd L. , Dombrowski Nina , Davín Adrián A. , Pisani Davide , Donoghue Philip C. J. , Szöllősi Gergely J. , Williams Tom A. , Spang Anja 
Published: April 2023

AbstractThe timing of early cellular evolution from the divergence of Archaea and Bacteria to the origin of eukaryotes remains poorly constrained. The ATP synthase complex is thought to have originated prior to the Last Universal Common Ancestor (LUCA) and analyses of ATP synthase genes, together with ribosomes, have played a key role in inferring and rooting the tree of life. Here we reconstruct the evolutionary history of ATP synthases using an expanded sampling of Archaea, Bacteria, and eukaryotes. We developed a phylogenetic cross-bracing approach making use of endosymbioses and ancient gene duplications of the major ATP synthase subunits to infer a highly resolved, dated species tree and establish an absolute timeline for ATP synthase evolution. Our analyses show that the divergence of the ATP synthase into F- and A/V-type lineages, was a very early event in cellular evolution dating back to more than 4Ga potentially predating the diversification of Archaea and Bacteria. Our cross-braced, dated tree of life also provides insight into more recent evolutionary transitions including eukaryogenesis, showing that the eukaryotic nuclear and mitochondrial lineages diverged from their closest archaeal (2.67-2.19Ga) and bacterial (2.58-2.12Ga) relatives at roughly the same time, with the nuclear stem being moderately longer.