bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Statistical Model for Inference of Recent and Incident HIV Infection Using Surveillance Data on Individuals Newly Diagnosed With HIV Infection in Scotland
Authors: McDonald Scott A. , Yeung Alan , Nandwani Rak , Clutterbuck Daniel , Wallace Lesley A. , Cullen Beth L. , Shepherd Samantha J. , Roy Kirsty , Marsh Kimberly , Gunson Rory , Hutchinson Sharon J. 
Published: June 2024

Background:
To inform global ambitions to end AIDS, evaluation of progress toward HIV incidence reduction requires robust methods to measure incidence. Although HIV diagnosis date in routine HIV/AIDS surveillance systems are often used as a surrogate marker for incidence, it can be misleading if acquisition of transmission occurred years before testing. Other information present in data such as antibody testing dates, avidity testing result, and CD4 counts can assist, but the degree of missing data is often prohibitive.

Methods:
We constructed a Bayesian statistical model to estimate the annual proportion of first ever HIV diagnoses in Scotland (period 2015–2019) that represent recent HIV infection (ie, occurring within the previous 3–4 months) and incident HIV infection (ie, infection within the previous 12 months), by synthesizing avidity testing results and surveillance data on the interval since last negative HIV test.

Results:
Over the 5-year analysis period, the model-estimated proportion of incident infection was 43.9% (95% CI: 40.9 to 47.0), and the proportion of recent HIV infection was 21.6% (95% CI: 19.1 to 24.1). Among the mode of HIV acquisition categories, the highest proportion of recent infection was estimated for people who inject drugs: 27.4% (95% CI: 20.4 to 34.4).

Conclusions:
The Bayesian approach is appropriate for the high prevalence of missing data that can occur in routine surveillance data sets. The proposed model will aid countries in improving their understanding of the number of people who have recently acquired their infection, which is needed to progress toward the goal of HIV transmission elimination.
Randomized Controlled Trial of Enhanced Recovery After Surgery Protocols in Live Kidney Donors: ERASKT Study
Authors: Saks Jacob , Yoon Uzung , Neiswinter Natalie , Schwenk Eric S. , Goldberg Stephen , Nguyen Linh , Torjman Marc C. , Elia Elia , Shah Ashesh 
Published: June 2024

Background:
Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function.

Methods:
In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis plane block. Our primary outcome measure was postoperative opioid consumption. The secondary outcome measures were postoperative pain scores, first oral intake, and hospital length of stay.

Results:
There were no significant differences in demographics between the 2 groups. The ERAS group had a statistically significant reduction in total postoperative opioid consumption calculated in intravenous morphine equivalents (24.2 ± 20.2 versus 71 ± 39.5 mg, P < 0.01). Postoperative pain scores were significantly lower (P < 0.001) from 1 h postoperatively to 48 h. Surgical time was 45 min shorter (P = 0.037). Intraoperative PlasmaLyte administration was lower (PlasmaLyte: 1444 ± 907 versus 2168 ± 1347 mL, P = 0.049). Time to tolerating regular diet was shorter by 2 h (P < 0.008), and length of hospital stay was decreased by 10.1 h.

Conclusions:
The ERAS group experienced superior postoperative analgesia and a shorter length of hospital stay compared with controls.
Colony pattern development of a synthetic bistable switch
Authors: Chu Pan , Zhu Jingwen , Ma Zhixin , Fu Xiongfei 
Published: June 2024

AbstractMicrobial colony development hinges upon a myriad of factors, including mechanical, biochemical, and environmental niches, which collectively shape spatial patterns governed by intricate gene regulatory networks. The inherent complexity of this phenomenon necessitates innovative approaches to comprehend and compare the mechanisms driving pattern formation. Here, we unveil the multistability of bacterial colony patterns orchestrated by a simple synthetic bistable switch. Utilizing quantitative imaging and spatially resolved transcriptome approaches, we explore the deterministic process of a ring-like colony pattern formation from a single cell. This process is primarily driven by bifurcation events programmed by the gene regulatory network and microenvironmental cues. Additionally, we observe a noise-induced process amplified by the founder effect, leading to patterns of symmetry-break during range expansion. The degrees of asymmetry are profoundly influenced by the initial conditions of single progenitor cells during the nascent stages of colony development. These findings underscore how the process of range expansion enables individual cells, exposed to a uniform growth-promoting environment, to exhibit inherent capabilities in generating emergent, self-organized behaviour.
Head dopaminergic and serotonergic neurons monitor alterations in gut bacterial activity through a gut-brain-gut axis
Authors: Li Guanqun , Wu Yangyang , Huang Xiaowen , Du Minghui , Tang Hongyun 
Published: June 2024

AbstractThe brain is suggested to monitor gut microbial changes to critically maintain health, whereas the particular bacterial alterations and the mechanisms involved are largely unclear. Here, through a genome-wide screen, we identified 29E. coligenes whose inactivation can be surveilled byC. eleganshead dopaminergic and serotonergic neurons through increasing host neuronal dopamine and serotonin biosynthesis. Mechanistically, we found that these head neurons respond to theE. colilack of respiratory chain genes by detecting the bacteria-caused reductions in host labile iron levels that impair intestinal mitochondria, and the intestine-expressed mitochondrial stress sensor ATFS-1 is critically involved. Furthermore, this neuronal response in turn promotes intestinal ferritin-1 expression to counteract bacteria-caused labile iron reduction and thereby maintaining mitochondrial function. Our findings systematically identify bacterial activity changes that elevate brain dopamine and serotonin levels and unveil an unexpected gut-brain-gut axis in which the head neurons inspect bacterial activity-mediated changes in host iron metabolism and mitochondrial function, enlightening crucial roles and mechanisms of brain in surveilling microbial activity alterations.
Transcriptome analysis ofDrosophila suzukiireveals molecular mechanisms conferring pyrethroid and spinosad resistance
Authors: Tabuloc Christine A. , Carlson Curtis R. , Ganjisaffar Fatemeh , Truong Cindy C. , Chen Ching-Hsuan , Lewald Kyle M. , Hidalgo Sergio , Nicola Nicole L. , Jones Cera E. , Sial Ashfaq A. , Zalom Frank G. , Chiu Joanna C. 
Published: June 2024

AbstractDrosophila suzukiilay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach forD. suzukiimanagement, resulting in detections of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveragedD. melanogastermutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistantD. suzukiito demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance inD. suzukiiand provides insights into how current management practices can be optimized.
Spatial Transcriptomics Prediction from Histology Images at Single-cell Resolution using RedeHist
Authors: Zhong Yunshan , Zhang Jiaxiang , Ren Xianwen 
Published: June 2024

AbstractSpatial transcriptomics (ST) offers substantial promise in elucidating the tissue architecture of biological systems. However, its utility is frequently hindered by constraints such as high costs, time-intensive procedures, and incomplete gene readout. Here we introduce RedeHist, a novel deep learning approach integrating scRNA-seq data to predict ST from histology images at single-cell resolution. Application of RedeHist to both sequencing-based and imaging-based ST data demonstrated its outperformance in high-resolution and accurate prediction, whole-transcriptome gene imputation, and fine-grained cell annotation compared with the state-of-the-art algorithms.
Common and unique neurophysiological signatures for the stopping and revising of actions reveal the temporal dynamics of inhibitory control
Authors: Hervault Mario , Wessel Jan R. 
Published: June 2024

AbstractInhibitory control is a crucial cognitive-control ability for behavioral flexibility that has been extensively investigated through action-stopping tasks. Multiple neurophysiological features have been proposed to represent ‘signatures’ of inhibitory control during action-stopping, though the processes signified by these signatures are still controversially discussed. The present study aimed to disentangle these processes by comparing simple stopping situations with those in which additional action revisions were needed. Three experiments in female and male humans were performed to characterize the neurophysiological dynamics involved in action-stopping and - changing, with hypotheses derived from recently developed two-stage ‘pause-then-cancel’ models of inhibitory control. Both stopping and revising an action triggered an early broad ‘pause’-process, marked by frontal EEG β-bursts and non-selective suppression of corticospinal excitability. However, partial-EMG responses showed that motor activity was only partially inhibited by this ‘pause’, and that this activity can be further modulated during action-revision. In line with two-stage models of inhibitory control, subsequent frontocentral EEG activity after this initial ‘pause’ selectively scaled depending on the required action revisions, with more activity observed for more complex revisions. This demonstrates the presence of a selective, effector-specific ‘retune’ phase as the second process involved in action-stopping and -revision. Together, these findings show that inhibitory control is implemented over an extended period of time and in at least two phases. We are further able to align the most commonly proposed neurophysiological signatures to these phases and show that they are differentially modulated by the complexity of action-revision.Significance StatementInhibitory control is one of the most important control processes by which humans can regulate their behavior. Multiple neurophysiological signatures have been proposed to reflect inhibitory control. However, these play out on different time scales and appear to reflect different aspects of cognitive control, which are controversially debated.Recent two-stage models of inhibitory control have proposed that two phases implement the revisions of actions: ‘pause’ and ‘retune’. Here, we provide the first empirical evidence for this proposition: Action revisions engendered a common initial low-latency ‘pause’, during which motor activity is broadly suppressed. Later activity, however, distinguishes between simple stopping of actions and more complex action revisions. These findings provide novel insights into the sequential dynamics of human action control.
Methylation and Transcriptomic Profiling Reveals Short Term and Long Term Regulatory Responses in Polarized Macrophages
Authors: Migliaccio Giorgia , Morikka Jack , del Giudice Giusy , Vaani Maaret , Möbus Lena , Serra Angela , Federico Antonio , Greco Dario 
Published: June 2024

AbstractMacrophage plasticity allows the adoption of distinct functional states in response to environmental cues. While unique transcriptomic profiles define these states, focusing solely on transcription neglects potential long-term effects. The investigation of epigenetic changes can be used to understand how temporary stimuli can result in lasting effects. Moreover, epigenetic alterations play an important role in the pathophysiology of macrophages, including phenomena related to the trained innate immunity, which allow faster and more efficient inflammatory responses upon subsequent encounters with the same pathogen. In this study, we used a multi-omics approach to elucidate the interplay between gene expression and DNA-methylation, unravelling the long-term effects of diverse polarizing environments on macrophage activity. We identified a common core set of genes that are differentially methylated regardless of exposure suggesting a potential mechanism for rapid adaptation to various stimuli. These conserved epigenetic modifications might represent a fundamental state that allows for flexible responses to various environmental cues. Functional analysis revealed that processes requiring rapid responses displayed transcriptomic regulation, whereas functions critical for long-term adaptations exhibited co-regulation at both transcriptomic and epigenetic levels. Our study unveils a novel set of genes critically linked to the long-term effects of macrophage polarization. This discovery underscores the potential of epigenetics in elucidating how macrophages establish long-term memory and influence health outcomes.Highlights:- Environmental signals trigger gene changes in macrophages, leaving a long-lasting epigenetic reprogramming- Epigenetic changes and metabolic shifts in polarized macrophages suggest training mechanisms- Common gene set epigenetically altered across different cues, suggest common adaptation to various stimuliGraphical Abstract
CRISPRware: an efficient method for contextual gRNA library design
Authors: Malekos Eric , Montano Christy , Carpenter Susan 
Published: June 2024

AbstractWe present CRISPRware, an efficient method for generating guide RNA (gRNA) libraries against transcribed, translated, and noncoding regions. CRISPRware leverages next-generation sequencing data to design context-specific gRNAs and accounts for genetic variation, which allows allele-specific guide design on a genome-wide scale. The latter ability holds promise for the development of gene therapy in the context of gene dosing and dominant negative mutations.
Pharmacologic Inhibition of Ferroptosis Attenuates Experimental Abdominal Aortic Aneurysm Formation
Authors: Krebs Jonathan R. , Bellotti Paolo , Valisno Jeff Arni C. , Su Gang , Sharma Shiven , Kollareth Denny Joseph Manual , Hartman Joseph B. , Adithan Aravinthan , Spinosa Michael , Kamat Manasi , Garrett Timothy , Cai Guoshuai , Sharma Ashish K. , Upchurch Gilbert R. 
Published: June 2024

ABSTRACTThe pathogenesis of abdominal aortic aneurysm (AAA) formation involves vascular inflammation, thrombosis formation and programmed cell death leading to aortic remodeling. Recent studies have suggested that ferroptosis, an excessive iron-mediated cell death, can regulate cardiovascular diseases, including AAAs. However, the role of ferroptosis in immune cells, like macrophages, and ferroptosis-related genes in AAA formation remains to be deciphered. Single cell-RNA sequencing of human aortic tissue from AAA patients demonstrates significant differences in ferroptosis-related genes compared to control aortic tissue. Using two established murine models of AAA and aortic rupture in C57BL/6 (WT) mice, we observed that treatment with liproxstatin-1, a specific ferroptosis inhibitor, significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), increased smooth muscle cell α-actin expression and elastic fiber disruption compared to mice treated with inactivated elastase in both pre-treatment and treatment after a small AAA had already formed. Lipidomic analysis using mass spectrometry shows a significant increase in ceramides and a decrease in intact lipid species levels in murine tissue compared to controls in the chronic AAA model on day 28. Mechanistically,in vitrostudies demonstrate that liproxstatin-1 treatment of macrophages mitigated the crosstalk with aortic smooth muscle cells (SMCs) by downregulating MMP2 secretion. Taken together, this study demonstrates that pharmacological inhibition by liproxstatin-1 mitigates macrophage-dependent ferroptosis contributing to inhibition of aortic inflammation and remodeling during AAA formation.
A potent agonist-based PROTAC targeting Pregnane X Receptor that delays colon cancer relapse
Authors: Bansard Lucile , Laconde Guillaume , Delfosse Vanessa , Huet Tiphaine , Ayeul Margaux , Rigal Emilie , Donati Quentin , Gerbal-Chaloin Sabine , Daujat-Chavanieu Martine , Legrand Baptiste , Chavanieu Alain , Martin Anthony R. , Pannequin Julie , Bourguet William , Amblard Muriel , Pascussi Jean Marc 
Published: June 2024

ABSTRACTTumor recurrence is often attributed to drug-tolerant cancer stem cells. We previously demonstrated that down regulation of the Pregnane X Receptor (PXR, NR1I2) decreases chemoresistance of cancer stem cells and prevents colorectal cancer recurrence in xenograft mouse models. These is a lack of PXR antagonists that are appropriate for clinical use. In this study, we report the design and synthesis of a novel PXR agonist-based PROTAC (JMV7048) that induces polyubiquitination and degradation of human PXR protein in an E3 CRBN ubiquitin ligase- and the 26S proteasome-dependent manner. This molecule specifically degrades PXR in colon carcinoma, hepatoma, and pancreatic cancer cell lines, but not in primary cultures of human hepatocytes. Crucially, JMV7048 decreased PXR protein expression in colon cancer stem cells and sensitized them to chemotherapy significantly delaying cancer relapsein vivo.PROTACs targeting PXR protein could thus become novel therapeutic agents to enhance cancer cell sensitivity to chemotherapy.
Consolidated Calcium kinetic rates in a Caucasian population as a function of age and sex
Authors: Hartung Niklas , A Abrams Steven , Huisinga Wilhelm , Weisser Karin 
Published: June 2024

ABSTRACTCalcium plays an important role in bone physiology and its kinetics change over lifetime. The analysis of calcium deposition and resorption through stable isotope techniques has guided recommendations on nutritional uptake for overall health. In addition, calcium kinetics have great relevance for toxicokinetic studies of bone-seeking elements (e.g, aluminium and lead) since these elements use common uptake and release pathways. While the impact of many factors on calcium kinetics have been investigated individually, a consolidated age- and sex-dependent kinetic description amenable for toxicokinetic modeling, however, is still lacking. Motivated by this need, we systematically reviewed the existing literature on calcium kinetics and assembled a large and consistent dataset. Then, building on the work of O’Flaherty in the 1990s, we formulated age- and sex-dependent functions describing calcium deposition, resorption, net retention, and mass. This description represents the current knowledge on calcium kinetics in a reference individual of Caucasians as most data was from this population.
RNAfold: RNA tertiary structure prediction using variational autoencoder
Authors: Kazanskii M.A. , Uroshlev L. , Zatylkin F. , Pospelova I. , Kantidze O. , Gankin Y. 
Published: June 2024

AbstractUnderstanding the RNA tertiary structure is crucial for advancing therapeutic development and vaccine design. Previous methods, such as dynamic simulations, have been used to study RNA structure. However, these methods often struggle to capture the complex non-linear relationships in RNA sequences. Other approaches focused on simple models, resulting in lower performance. Indeed, one of the main challenges in predicting RNA tertiary structure is the lack of data, and using complicated algorithms is limited. In this paper, we introduce the Variational Autoencoder (VAE). In this paper, we introduce the Variational Autoencoder (VAE) for the problem of RNA folding and demonstrate that the Variational Autoencoder could yield promising results. Our model achieves a Root Mean Square Error (RMSE) of approximately 3.3Å in predicting nucleotide positions, significantly outperforming existing approaches.
UltraCortex: Submillimeter Ultra-High Field 9.4 T Brain MR Image Collection and Manual Cortical Segmentations
Authors: Mahler Lucas , Steiglechner Julius , Bender Benjamin , Lindig Tobias , Ramadan Dana , Bause Jonas , Birk Florian , Heule Rahel , Charyasz Edyta , Erb Michael , Jangir Kumar Vinod , E Hagberg Gisela , Martin Pascal , Lohmann Gabriele , Scheffler Klaus 
Published: June 2024

ABSTRACTTheUltraCortexrepository (https://www.ultracortex.org) houses magnetic resonance imaging data of the human brain obtained at an ultra-high field strength of 9.4 T. It contains 86 structural MR images with spatial resolutions ranging from 0.6 to 0.8 mm. Additionally, the repository includes segmentations of 12 brains into gray and white matter compartments. These segmentations have been independently validated by two expert neuroradiologists, thus establishing them as a reliable gold standard. This resource provides researchers with access to high-quality brain imaging data and validated segmentations, facilitating neuroimaging studies and advancing our understanding of brain structure and function. Existing repositories do not accommodate field strengths beyond 7 T, nor do they offer validated segmentations, underscoring the significance of this new resource.
An improved method for sampling and quantitative protein analytics of cerebrospinal fluid of single mice
Authors: Lourbopoulos Athanasios , Müller Stephan A. , Jocher Georg , Wick Manfred , Plesnila Nikolaus , Lichtenthaler Stefan F. 
Published: June 2024

AbstractMice are the most commonly used preclinical animal model, but protein analytics of murine cerebrospinal fluid (CSF) remains challenging because of low CSF volume (often <10 µl) and frequent blood contaminations. We developed an improved CSF sampling method that allows routine collection of increased volumes (20-30 µl) of pure CSF from individual mice, enabling multiple protein analytical assays from a single sample. Based on cell counts and hemoglobin ELISAs, we provide an easy quality control workflow for obtaining cell- and blood-free murine CSF. Through mass spectrometry-based proteomics using an absolutely quantified external standard, we estimated concentrations for hundreds of mouse CSF proteins. While repeated CSF sampling from the same mouse was possible, it induced CSF proteome changes. Applying the improved method, we found that the mouse CSF proteome remains largely stable over time in wild-type mice, but that amyloid pathology in the 5xFAD mouse model of Alzheimer’s disease massively changes the CSF proteome. Neurofilament light chain and TREM2, markers of neurodegeneration and activated microglia, respectively, were strongly upregulated and validated using immunoassays. In conclusion, our refined murine CSF collection method overcomes previous limitations, allowing multiple quantitative protein analyses for applications in biomedicine.