bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Does Target Lesion Selection Affect RECIST? A Computer Simulation Study
Authors: Tareco Bucho Teresa M. , Tissier Renaud L.M. , Groot Lipman Kevin B.W. , Bodalal Zuhir , Delli Pizzi Andrea , Nguyen-Kim Thi Dan Linh , Beets-Tan Regina G.H. , Trebeschi Stefano 
Published: November 2023

Objectives
Response Evaluation Criteria in Solid Tumors (RECIST) is grounded on the assumption that target lesion selection is objective and representative of the change in total tumor burden (TTB) during therapy. A computer simulation model was designed to challenge this assumption, focusing on a particular aspect of subjectivity: target lesion selection.

Materials and Methods
Disagreement among readers and the disagreement between individual reader measurements and TTB were analyzed as a function of the total number of lesions, affected organs, and lesion growth.

Results
Disagreement rises when the number of lesions increases, when lesions are concentrated on a few organs, and when lesion growth borders the thresholds of progressive disease and partial response. There is an intrinsic methodological error in the estimation of TTB via RECIST 1.1, which depends on the number of lesions and their distributions. For example, for a fixed number of lesions at 5 and 15, distributed over a maximum of 4 organs, the error rates are observed to be 7.8% and 17.3%, respectively.

Conclusions
Our results demonstrate that RECIST can deliver an accurate estimate of TTB in localized disease, but fails in cases of distal metastases and multiple organ involvement. This is worsened by the “selection of the largest lesions,” which introduces a bias that makes it hardly possible to perform an accurate estimate of the TTB. Including more (if not all) lesions in the quantitative analysis of tumor burden is desirable.
Cortical network mechanisms in subcallosal cingulate deep brain stimulation for depression
Authors: Scherer M , Harmsen IE , Samuel N , Elias GJB , Germann J , Boutet A , MacLeod CE , Giacobbe P , Rowland NC , Lozano AM , Milosevic L 
Published: November 2023

AbstractIdentifying functional biomarkers of clinical success can contribute to therapy optimization, and provide insights into the pathophysiology of treatment-resistant depression and mechanisms underlying the potential restorative effects of subcallosal cingulate deep brain stimulation.Magnetoencephalography data were obtained from 15 individuals who underwent subcallosal cingulate deep brain stimulation for treatment-resistant depression and 25 healthy subjects. The first objective herein was to identify region-specific oscillatory modulations for the identification of discriminative network nodes expressing (i) pathological differences in TRD (responders and non-responders, stimulation-OFF) compared to healthy subjects, which (ii) were counteracted by stimulation in a responder-specific manner. The second objective of this work was to further explore the mechanistic effects of stimulation intensity and frequency.Oscillatory power analyses led to the identification of discriminative regions that differentiated responders from non-responders based on modulations of increased alpha (8-12 Hz) and decreased gamma (32-116 Hz) power within nodes of the default mode, central executive, and somatomotor networks, Broca’s area, and lingual gyrus. Within these nodes, it was also found that low stimulation frequency had stronger effects on oscillatory modulation than increased stimulation intensity.The identified discriminative network profile implies modulation of pathological activities in brain regions involved in emotional control/processing, motor control, and the interaction between speech, vision, and memory, which have all been implicated in depression. This modulated network profile may represent a functional substrate for therapy optimization. Stimulation parameter analyses revealed that oscillatory modulations can be strengthened by increasing stimulation intensity or, to an even greater extent, by reducing frequency.
From connectome to effectome: learning the causal interaction map of the fly brain
Authors: Pospisil Dean A. , Aragon Max J. , Dorkenwald Sven , Matsliah Arie , Sterling Amy R. , Schlegel Philipp , Yu Szi-chieh , McKellar Claire E. , Costa Marta , Eichler Katharina , Jefferis Gregory S.X.E. , Murthy Mala , Pillow Jonathan W. 
Published: November 2023

AbstractA long-standing goal of neuroscience is to obtain a causal model of the nervous system. This would allow neuroscientists to explain animal behavior in terms of the dynamic interactions between neurons. The recently reported whole-brain fly connectome [1–7] specifies the synaptic paths by which neurons can affect each other but not whether, or how, they do affect each other in vivo. To overcome this limitation, we introduce a novel combined experimental and statistical strategy for efficiently learning a causal model of the fly brain, which we refer to as the “effectome”. Specifically, we propose an estimator for a dynamical systems model of the fly brain that uses stochastic optogenetic perturbation data to accurately estimate causal effects and the connectome as a prior to drastically improve estimation efficiency. We then analyze the connectome to propose circuits that have the greatest total effect on the dynamics of the fly nervous system. We discover that, fortunately, the dominant circuits significantly involve only relatively small populations of neurons—thus imaging, stimulation, and neuronal identification are feasible. Intriguingly, we find that this approach also re-discovers known circuits and generates testable hypotheses about their dynamics. Overall, our analyses of the connectome provide evidence that global dynamics of the fly brain are generated by a large collection of small and often anatomically localized circuits operating, largely, independently of each other. This in turn implies that a causal model of a brain, a principal goal of systems neuroscience, can be feasibly obtained in the fly.
CC-seq: Nucleotide-resolution mapping of Spo11 DNA double-strand breaks inS. cerevisiaecells
Authors: Brown George G. B. , Gittens William H. , Allison Rachal M. , Oliver Antony W. , Neale Matthew J 
Published: November 2023

i.SummaryDuring meiosis Spo11 generates DNA double-strand breaks to induce recombination, becoming covalently attached to the 5′ ends on both sides of the break during this process. Such Spo11 “covalent complexes” are transient in wild-type cells, but accumulate in nuclease mutants unable to initiate repair. The CC-seq method presented here details how to map the location of these Spo11 complexes genome-wide with strand-specific nucleotide-resolution accuracy in synchronisedSaccharomyces cerevisiaemeiotic cells.
Improving bacterial metagenomic research through long read sequencing
Authors: Greenman Noah , Hassouneh Sayf Al-Deen , Abdelli Latifa S. , Johnston Catherine , Azarian Taj 
Published: November 2023

AbstractMetagenomic sequencing analysis is central to investigating microbial communities in clinical and environmental studies. Short read sequencing remains the primary data type for metagenomic research, however, long read sequencing promises advantages of improved metagenomic assembly and resolved taxonomic identification. To assess the comparative performance of short and long read sequencing data for metagenomic analysis, we simulated short and long read datasets using increasingly complex metagenomes comprised of 10, 20, and 50 microbial taxa. In addition, an empirical dataset of paired short and long read data from mouse fecal pellets was generated to assess feasibility. We compared metagenomic assembly quality, taxonomic classification capabilities, and metagenome-assembled genome recovery rates for both simulated and real metagenomic sequence data. We show that long read sequencing data significantly improves taxonomic classification capabilities and assembly quality. For simulated long read datasets, metagenomic assemblies were completer and more contiguous with higher rates of metagenome-assembled genome recovery. This resulted in more precise taxonomic classifications. Analysis of empirical data demonstrated that sequencing technology directly affects compositional results. Overall, we highlight strengths of long read sequencing for metagenomic studies of microbial communities over traditional short read approaches. Long read sequencing improved the accuracy of classification and abundance estimation. These results will aid researchers when considering which sequencing platforms to use for metagenomic projects.Data descriptionThe experimental metagenomic sequence data used for comparison of short and long read data from the same source are available from NCBI’s Sequence Read Archive (SRA) under Bioproject accession ID PRJNA1092431.
Antimicrobial peptides and proteins as alternative antibiotics for porcine semen preservation
Authors: Ros-Santaella Jose Luis , Nový Pavel , Scaringi Maria , Pintus Eliana 
Published: November 2023

AbstractBackgroundAntimicrobial resistance (AMR) is nowadays a major emerging challenge for public health worldwide. The over- and misuse of antibiotics, including those for cell culture, are promoting AMR while also encouraging the research and employment of alternative drugs. The addition of antibiotics to the cell media is a must in sperm preservation, being gentamicin the most used for boar semen. Because of its continued use, several bacterial strains present in boar semen have developed resistance to this antibiotic. Antimicrobial peptides and proteins (AMPPs) are promising candidates as alternative antibiotics because their mechanism of action is less likely to promote AMR. In the present study, we tested two AMPPs (lysozyme and nisin; 50 and 500 µg/mL) as possible substitutes of gentamicin for boar semen preservation up to 48 h of storage.ResultsWe found that both AMPPs improved sperm plasma membrane and acrosome integrity during semen storage. The highest concentration tested for lysozyme also kept the remaining sperm parameters unaltered, at 48 h of semen storage, and reduced the bacterial load at comparable levels of the samples supplemented with gentamicin (p>0.05). On the other hand, while nisin (500 µg/mL) reduced the total Enterobacteriaceae counts, it also decreased the rapid and progressive sperm population and the seminal oxidation-reduction potential (p<0.05).ConclusionsThe protective effect of lysozyme on sperm function together with its antimicrobial activity and inborn presence in body fluids, including semen and cervical mucus, makes this enzyme a promising antimicrobial agent for boar semen preservation.
Weakly alkaline conditions degrade aflatoxins through lactone ring opening
Authors: Sandlin Natalie , Lee Jiu , Zaccaria Marco , Domin Marek , Momeni Babak 
Published: November 2023

AbstractAflatoxins (AFs) are fungal metabolites that ubiquitously contaminate many common food crops and contribute to major foodborne diseases in humans and animals. The ability to remove AFs from common food and feed commodities will improve health standards and limit the economic impact inflicted by AF food contamination. Known chemical strategies have used strong acids and bases to remove contaminating AF, but these methods often lead to ecological waste issues downstream. In this study, we explore the application of weaker acidic and alkaline conditions to removes two types of AFs, AFB1and AFG2. We find that a pH 9 buffered environment reduces AFB1and AFG2by more than 50% and 95%, respectively, within 24 hours. We show that AF degradation is through lactone ring opening, which is a known cause of AF toxicity, and provide a potential structure of the AFG2degradation byproduct. Further, we confirm that incubation in the pH 9 environment reduces the genotoxicity of AFB1. Our findings indicate that a weakly alkaline environment may adequately detoxify AF-contaminated food or feed without the need to apply stronger or harsher basic conditions.
Cost-utility analysis of low-dose pioglitazone in a population with prediabetes and a history of stroke and TIA
Authors: Yuan Fei , Spence J. David , Tarride Jean-Eric 
Published: November 2023

AbstractBACKGROUNDAmong patients with type 2 diabetes and a history of strokes or transient ischemic attacks, pioglitazone significantly reduces the risk of recurrent stroke. The Insulin Resistance Intervention in Stroke (IRIS) trial found that pioglitazone also reduced the risks of stroke or transient ischemic attacks and new-onset diabetes among patients with insulin resistance. As reported by our previous work, the low-dose pioglitazone was found to provide most of the clinical benefit of high-dose pioglitazone, with fewer adverse effects. We report a model-based economic evaluation to determine the cost-effectiveness of the low-dose pioglitazone versus placebo.METHODSA lifetime Markov model, with an annual cycle length and five health states (event-free, myocardial infarction, stroke, new-onset diabetes, death), was developed. Transition probabilities were extracted from a subgroup of IRIS patients with insulin resistance, defined by a glycosylated hemoglobin level of 5.7% to 6.4% (mean follow-up of 5 years). Health state costs and utilities were based on public sources and literature data, respectively. Utilities were weighted by time spent in health states to calculate quality-adjusted life years (QALYs). The incremental cost per QALY gained was estimated for the population. Annual discount rates of 0%, 1.5%, and 3% were applied. In addition to deterministic analyses, probabilistic sensitivity analyses were conducted to deal with parameter uncertainty. The analyses were conducted from a Canadian public payer perspective in 2023 Canadian dollars.RESULTSThe base case results indicated that over a lifetime, the expected costs were CAN$31,534 for low-dose pioglitazone and CAN$55,076 for placebo, resulting in a cost saving of CAN$23,542 in favor of the low-dose pioglitazone. Expected QALYs were 25.10 for the low-dose pioglitazone daily and 19.32 for placebo, resulting in a difference of 5.78 QALYs in favor of low-dose pioglitazone. Probability sensitivity analyses with varying discount rates confirmed these results.CONCLUSIONSCompared with placebo, low-dose pioglitazone is the dominant strategy.Key PointsQuestionCompared with a placebo, is low-dose pioglitazone cost-effective in treating stroke/ transient ischemic attack (TIA) and new-onset diabetes in a simulated population with prediabetics?FindingsOver a lifetime, the expected costs were CAN$31,534 for low-dose pioglitazone and CAN$55,076 for placebo, resulting in a cost saving of CAN$23,542 in favor of low-dose pioglitazone. Expected QALYs were 25.10 for low-dose pioglitazone daily and 19.32 for placebo, resulting in a difference of 5.78 QALYs in favor of low-dose pioglitazone. Sensitivity and scenario analyses confirmed the results.MeaningThe model-based economic evaluation indicates that low-dose pioglitazone, compared with placebo, is the dominant strategy.
MolecularWebXR: Multiuser discussions about chemistry and biology in immersive and inclusive VR
Authors: Cortés Rodríguez Fabio J. , Frattini Gianfranco , Phloi-Montri Sittha , Pinto Meireles Fernando Teixeira , Terrien Danaé A. , Cruz-León Sergio , Dal Peraro Matteo , Schier Eva , Lindorff-Larsen Kresten , Limpanuparb Taweetham , Moreno Diego M. , Abriata Luciano A. 
Published: November 2023

AbstractMolecularWebXR is a new website for education, science communication and scientific peer discussion in chemistry and biology, based on modern web-based Virtual Reality (VR) and Augmented Reality (AR). With no installs as it is all web-served, MolecularWebXR enables multiple users to simultaneously explore, communicate and discuss concepts about chemistry and biology in immersive 3D environments, by manipulating and passing around objects with their bare hands and pointing at different elements with natural hand gestures. User may either be present in the same real space or distributed around the world, in the latter case talking naturally with each other thanks to built-in audio features. Although MolecularWebXR is most immersive when running in the web browsers of high-end AR/VR headsets, its WebXR core also allows participation by users with consumer devices such as smartphones, possibly inserted into cardboard goggles for deeper immersivity, or even in computers and tablets. MolecularWebXR comes with preset VR rooms that cover topics from general, inorganic and organic chemistry, biophysics and structural biology, and general biology; besides, new content can be added at will through moleculARweb’s PDB2AR tool or by contacting the lead authors. We verified MolecularWebXR’s ease of use and versatility by people aged 12-80 years old in entirely virtual sessions or in mixed real-virtual sessions at various science outreach events, in courses at the bachelor, masters and early doctoral levels, in scientific collaborations, and in conference lectures. MolecularWebXR is available for free use without registration athttps://molecularwebxr.org, and a blog post version of this preprint with embedded videos is available athttps://go.epfl.ch/molecularwebxr-blog-post.
Climate-Change Driven Decline of an Insect Pathogen Increases the Risk of Defoliation by a Forest Pest Insect
Authors: Liu Jiawei , Kyle Colin , Wang Jiali , Kotamarthi Rao , Koval William , Dwyer Greg 
Published: November 2023

AbstractThe effects of climate change on forest-defoliating insects are poorly understood, a problem that is especially urgent in the case of the spongy moth (formerly “the gypsy moth”,Lymantria dispar). For decades following its introduction in 1869, the spongy moth severely defoliated North American forests, but the introduction of the pathogenEntomophaga maimaigain 1989 drastically lowered defoliation levels.E. maimaiga, however, needs cool, moist conditions, whereas climate change is bringing hot, dry conditions to the range of the spongy moth. Here we use an empirically validated mathematical model to project that climate change will sharply reduceE. maimaigainfection rates, greatly increasing spongy moth defoliation. Recent data show that defoliation has strongly rebounded, supporting our projections. Our work shows that the effects of climate change on insect pathogens can have dire consequences for forests, and demonstrates the importance of understanding how climate change can alter species interactions.
Design of efficient artificial enzymes using crystallographically-enhanced conformational sampling
Authors: Rakotoharisoa Rojo V. , Seifinoferest Behnoush , Zarifi Niayesh , Miller Jack D.M. , Rodriguez Joshua M. , Thompson Michael C. , Chica Roberto A. 
Published: November 2023

AbstractThe ability to create efficient artificial enzymes for any chemical reaction is of great interest. Here, we describe a computational design method for increasing catalytic efficiency ofde novoenzymes to a level comparable to their natural counterparts without relying on directed evolution. Using structural ensembles generated from dynamics-based refinement against X-ray diffraction data collected from crystals of Kemp eliminases HG3 (kcat/KM125 M−1s−1) and KE70 (kcat/KM57 M−1s−1), we design from each enzyme ≤10 sequences predicted to catalyze this reaction more efficiently. The most active designs displaykcat/KMvalues improved by 100–250-fold, comparable to mutants obtained after screening thousands of variants in multiple rounds of directed evolution. Crystal structures show excellent agreement with computational models. Our work shows how computational design can generate efficient artificial enzymes by exploiting the true conformational ensemble to more effectively stabilize the transition state.
An adaptable plasmid scaffold for CRISPR-based endogenous tagging
Authors: Philip Reuben , Sharma Amit , Matellan Laura , Erpf Anna C. , Hsu Wen-Hsin , Tkach Johnny M. , Wyatt Haley D. M. , Pelletier Laurence 
Published: November 2023

AbstractEndogenous tagging makes it possible to study a protein’s localization, dynamics, and function within its native regulatory context. This is typically accomplished via CRISPR, which involves inserting a sequence encoding a functional tag into the reading frame of a gene. However, this process is often inefficient. Here, we introduce the “quickTAG,” or qTAG system, a versatile collection of optimized repair cassettes designed to make CRISPR-mediated tagging more accessible. By including a desired tag sequence linked to a selectable marker in the cassette, integrations can be quickly isolated post-editing. The core sequence scaffold within these constructs incorporates several key features that enhance flexibility and ease of use, such as: specific cassette designs for N- and C-terminus tagging; standardized cloning sequences to simplify the incorporation of homology arms for HDR or MMEJ-based repairs; restriction sites next to each genetic element within the cassette for easy modification of tags and selectable markers; and the inclusion of lox sites flanking the selectable marker to allow for marker gene removal following integration. We showcase the versatility of these cassettes with a diverse range of tags, demonstrating their applications in fluorescence imaging, proximity-dependent biotinylation, epitope tagging, and targeted protein degradation. The adaptability of this scaffold is also exhibited by incorporating novel tags such as mStayGold, which offer enhanced brightness and photostability, reconciling prolonged live-cell imaging of proteins at their endogenous levels. Finally, by leveraging the restriction sites, entirely distinct cassette structures and editing schemes were developed. These enabled scenarios that included conditional expression tagging, selectable knockout tagging, and safe-harbor expression. Our existing and forthcoming collection of plasmids will be accessible through Addgene. It includes ready-to-use constructs targeting common subcellular marker genes, as well as an assortment of tagging cassettes for the tagging of genes of interest. The qTAG system offers an accessible framework to streamline endogenous tagging and will serve as an open resource for researchers to adapt and tailor for their own experiments.