bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating antiretroviral therapy–induced insulin resistance syndrome using the homeostasis model assessment method: an important global clarion call for concern among people living with HIV-disease
Authors: Fasipe Olumuyiwa John , Ayoade Olufisayo Gabriel , Enikuomehin Adenike Christiana , Falade Catherine Olufunke 
Published: June 2024

Abstract

Background
Antiretroviral treatment advances have been accompanied by a new spectrum of adverse drug reactions that affect metabolism and body composition.

Purpose
This review was principally designed to focus on how to comprehensively evaluate for the occurrence of antiretroviral therapy-induced insulin resistance syndrome with associated impaired glucose metabolism disorder(s) among people living with HIV disease.

Data sources and materials
During the course of this present study, original peer-reviewed articles reported in English language that investigated antiretroviral therapy-induced insulin resistance were identified by exploring the Medline-Entrez-PubMed search, Web of Science database, Google Scholar search, and Science Direct database online facilities. Also, information was sourced from printed textbooks and the reports documented by some recognized medically inclined and health professional bodies. These published materials containing documented reports relating to the subject matter of focus in this review were accessed and adequately referenced. This study spanned for 12-month duration from March 2023 to February 2024.

Study selection and manuscript preparation with limitations
A total number of 92 published articles were reviewed, out of which 55 referenced articles were found to contain information pertinent to this present study; while those parts of the referenced articles inapt to this study were neglected. Antiretroviral therapy-induced insulin resistance syndrome can be broadly classified into mild, moderate, and severe categories; based on the severity grading reviews of homeostasis model assessment-insulin resistance index values.

Conclusion
The clinical assessment of antiretroviral therapy-induced insulin resistance syndrome should be given utmost importance in HIV-disease individuals with considerably high-risk factor(s) for its occurrence.
Corticostriatal ensemble dynamics across heroin self-administration to reinstatement
Authors: Clarke Rachel E. , Grant Roger I. , Woods Shannon N. , Pagoota Bayleigh E. , Buchmaier Sophie , Bordieanu Bogdan , Tsyrulnikov Anna , Westphal Annaka M. , Paniccia Jacqueline E , Doncheck Elizabeth M , Carroll-Deaton Jayda , Vollmer Kelsey M , Ward Amy L. , Winston Kion T. , King Danielle I. , Baek Jade , Martino Mike R. , Green Lisa M. , McGinty Jacqueline F. , Scofield Michael D. , Otis James M. 
Published: June 2024

ABSTRACTCorticostriatal projection neurons from prelimbic medial prefrontal cortex to the nucleus accumbens core critically regulate drug-seeking behaviors, yet the underlying encoding dynamics whereby these neurons contribute to drug seeking remain elusive. Here we use two-photon calcium imaging to visualize the activity of corticostriatal neurons in mice from the onset of heroin use to relapse. We find that the activity of these neurons is highly heterogeneous during heroin self-administration and seeking, with at least 8 distinct neuronal ensembles that display both excitatory and inhibitory encoding dynamics. These neuronal ensembles are particularly apparent during relapse, where excitatory responses are amplified compared to heroin self-administration. Moreover, we find that optogenetic inhibition of corticostriatal projection neurons attenuates heroin seeking regardless of the relapse trigger. Our results reveal the precise corticostriatal activity dynamics underlying drug-seeking behaviors and support a key role for this circuit in mediating relapse to drug seeking.
Enhancing PDAC Therapy: Decitabine-Olaparib Synergy Targets KRAS-Dependent Tumors
Authors: Anastasio Giorgia , Felaco Michela , Lamolinara Alessia , del Pizzo Francesco , Cacciagrano Elisa , Mottini Carla , Mutarelli Margherita , Di Modugno Francesca , Iezzi Manuela , Cardone Luca 
Published: June 2024

SUMMARYCurrent chemotherapies provide limited clinical benefits to patients with pancreatic ductal adenocarcinoma (PDAC), partly due to the lack of effective biomarkers for personalized therapy. KRAS activating mutations occur in almost 90% of PDAC cases, leading to a subset of tumorsdependent onKRASfor survival (dKRAS). Assessing dKRAS in PDAC can be achieved using gene expression signature scores, independent of specific KRAS mutations, allowing for personalized therapies. Previous studies have shown that dKRAS-PDAC cells are more sensitive to the FDA-approved drug decitabine (DEC), although the mechanism remains unclear. While DEC is approved for hematological tumors, its repurposing in solid tumors poses challenges due to high-dose hematological side effects. Identifying optimal pharmacological approaches and response biomarkers is crucial for the successful clinical implementation of DEC in PDAC and other solid tumors. Our investigation revealed that low-dose DEC combined with the PARP inhibitor olaparib (OLA) enhances antitumor activity in dKRAS-PDAC. Mechanistically, DEC induces DNA damage and activates an ATR/ATM-mediated DNA damage response (DDR), with PARP1-mediated DNA repair playing a crucial role. Inhibiting PARP activity with OLA enhances antitumor activity, even inBRCA1/2wild-typeand homologous recombination (HR)-proficient tumors, but it is ineffective in KRAS-independent tumors. Thus, transcriptomic-based KRAS dependency scores effectively predict the efficacy of combined therapy. Additionally, in dKRAS-PDAC tumors carrying aBRCA2mutation, low-dose DEC enhances OLA’s antitumor activity, completely inhibiting metastasis growth compared to single-drug treatments. Our findings support further clinical evaluation of DEC+OLA combination therapy in PDAC, particularly in dKRAS-positive tumors, irrespective of BRCA1/2 status. This approach extends the clinical benefit of OLA beyond BRCA status, addressing a limitation in targeted PARP inhibitor therapies. Furthermore, we highlight DDR as a key mechanism of action for DEC, beyond its role in gene expression regulation, underscoring the mode of action of this widely used anticancer drug.
Mapping the impact of age and APOE risk factors for late onset Alzheimer’s disease on long range brain connections through multiscale bundle analysis
Authors: Stout Jacques , Anderson Robert J , Mahzarnia Ali , Han Zay , Beck Kate , Browndyke Jeffrey , Johnson Kim , O’Brien Richard J , Badea Alexandra 
Published: June 2024

AbstractAlzheimer’s disease currently has no cure and is usually detected too late for interventions to be effective. In this study we have focused on cognitively normal subjects to study the impact of risk factors on their long-range brain connections. To detect vulnerable connections, we devised a multiscale, hierarchical method for spatial clustering of the whole brain tractogram and examined the impact of age and APOE allelic variation on cognitive abilities and bundle properties including texture e.g., mean fractional anisotropy, variability, and geometric properties including streamline length, volume, and shape, as well as asymmetry. We found that the third level subdivision in the bundle hierarchy provided the most sensitive ability to detect age and genotype differences associated with risk factors. Our results indicate that frontal bundles were a major age predictor, while the occipital cortex and cerebellar connections were important risk predictors that were heavily genotype dependent, and showed accelerated decline in fractional anisotropy, shape similarity, and increased asymmetry. Cognitive metrics related to olfactory memory were mapped to bundles, providing possible early markers of neurodegeneration. In addition, physiological metrics such as diastolic blood pressure were associated with changes in white matter tracts. Our novel method for a data driven analysis of sensitive changes in tractography may differentiate populations at risk for AD and isolate specific vulnerable networks.
Reduction in olfactory ability in agingMitfmutant mice without neurodegeneration
Authors: Mechmet Fatich , Steingrímsson Eiríkur , Henry Petersen Pétur 
Published: June 2024

AbstractAge-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction, where the olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. Decline in olfaction is also associated with early symptoms of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the underlying reasons are unclear. The microphthalmia-associated transcription factor (MITF) is expressed in the projection neurons (PNs) of the OB – the mitral and tufted (M/T) cells. Primary M/T cells fromMitfmutant mice show hyperactivity, potentially attributed to reduced expression of a key potassium channel subunit,Kcnd3/Kv4.3. This influences intrinsic plasticity, an essential mechanism involving the non-synaptic regulation of neuronal activity. As neuronal hyperactivity often precedes neurodegenerative conditions, the current study aimed to determine whether the absence ofMitfhas degenerative effects during aging. AgedMitfmutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OB suggests that during aging compensatory mechanisms lead to stabilization.Significance statementThis study highlights the age-related decline in olfaction and elucidates compensatory mechanisms mediated by potassium channels. These findings improve our comprehension of the processes underlying age-related changes in olfaction.
Attenuated processing of vowels in the left hemisphere predicts speech-in-noise perception deficit in children with autism
Authors: Fadeev Kirill A. , Romero Reyes Ilacai V. , Goiaeva Dzerassa E. , Obukhova Tatiana S. , Ovsiannikova Tatiana M. , Prokofyev Andrey O. , Rytikova Anna M. , Novikov Artem Y. , Kozunov Vladimir V. , Stroganova Tatiana A. , Orekhova Elena V. 
Published: June 2024

ABSTRACTBackgroundDifficulties with speech-in-noise perception in autism spectrum disorders (ASD) may be associated with impaired analysis of speech sounds, such as vowels, which represent the fundamental phoneme constituents of human speech. Vowels elicit early (< 100 ms) sustained processing negativity (SPN) in the auditory cortex that reflects the detection of an acoustic pattern based on the presence of formant structure and/or periodic envelope information (f0) and its transformation into an auditory “object”.MethodsWe used magnetoencephalography (MEG) and individual brain models to investigate whether SPN is altered in children with ASD and whether this deficit is associated with impairment in their ability to perceive speech in the background of noise. MEG was recorded while boys with ASD and typically developing boys passively listened to sounds that differed in the presence/absence off0periodicity and formant structure. Word-in-noise perception was assessed in the separate psychoacoustic experiment using stationary and amplitude modulated noise with varying signal-to-noise ratio.ResultsSPN was present in both groups with similarly early onset. In children with ASD, SPN associated with processing formant structure was reduced predominantly in the cortical areas lateral to and medial to the primary auditory cortex, starting at ∼ 150 - 200 ms after the stimulus onset. In the left hemisphere, this deficit correlated with impaired ability of children with ASD to recognize words in amplitude-modulated noise, but not in stationary noiseConclusionsThese results suggest that perceptual grouping of vowel formants into phonemes is impaired in children with ASD and that, in the left hemisphere, this deficit contributes to their difficulties with speech perception in fluctuating background noise.
CD-GPT As a Biological Foundation Model Bridging the Gap between Molecular Sequences Through Central Dogma
Authors: Zhu Xiao , Qin Chenchen , Wang Fang , Yang Fan , He Bing , Zhao Yu , Yao Jianhua 
Published: June 2024

AbstractThe central dogma serves as a fundamental framework for understanding the flow and expression of genetic information within living organisms, facilitating the connection of diverse biological sequences across molecule types. In this study, we present CD-GPT (Central Dogma Generative Pretrained Transformer), a generative biological foundation model with 1 billion parameters, aiming to capture the sequence relationships between DNA, RNA, and proteins. We model sequences in a unified representational space and employ a shared, multi-molecule vocabulary to narrow their distances in the embedding space effectively. Through extensive pretraining on nucleotide and amino acid sequence data, CD-GPT exhibits exceptional performance in a wide range of predictive and generative downstream tasks, including mono-molecular and multi-molecular analyses. Notably, CD-GPT excels in tasks such as genomic element detection, protein property prediction, RNA-protein interaction identification and also generative tasks like protein generation and reverse translation. The versatility of CD-GPT opens up promising avenues for advanced multi-omics analysis.
BioMapAI: Artificial Intelligence Multi-Omics Modeling of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
Authors: Xiong Ruoyun , Aiken Elizabeth , Caldwell Ryan , Vernon Suzanne D. , Kozhaya Lina , Gunter Courtney , Bateman Lucinda , Unutmaz Derya , Oh Julia 
Published: June 2024

AbstractMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic illness with a multifactorial etiology and heterogeneous symptomatology, posing major challenges for diagnosis and treatment. Here, we present BioMapAI, a supervised deep neural network trained on a four-year, longitudinal, multi-omics dataset from 249 participants, which integrates gut metagenomics, plasma metabolomics, immune cell profiling, blood laboratory data, and detailed clinical symptoms. By simultaneously modeling these diverse data types to predict clinical severity, BioMapAI identifies disease- and symptom-specific biomarkers and robustly classifies ME/CFS in both held-out and independent external cohorts. Using an explainable AI approach, we construct the first connectivity map spanning the microbiome, immune system, and plasma metabolome in health and ME/CFS, adjusted for age, gender, and additional clinical factors. This map uncovers disrupted associations between microbial metabolism (e.g., short-chain fatty acids, branched-chain amino acids, tryptophan, benzoate), plasma lipids and bile acids, and heightened inflammatory responses in mucosal and inflammatory T cell subsets (MAIT, γδT) secreting IFNγ and GzA. Overall, BioMapAI provides unprecedented systems-level insights into ME/CFS, refining existing hypotheses and hypothesizing new pathways associated to the disease’s heterogeneous symptoms.
Unbiased and comprehensive identification of viral encoded circular RNAs in a large range of viral species and families
Authors: Chasseur Alexis S , Bellefroid Maxime , Galais Mathilde , Gong Meijiao , Mathieu Sarah , Ponsard Camille , Vreux Laure , Yague-Sanz Carlo , Dewals Benjamin G , Gillet Nicolas A , Muylkens Benoît , Van Lint Carine , Coupeau Damien 
Published: June 2024

AbstractNon-coding RNAs play a significant role in viral infection cycles, with recent attention focused on circular RNAs (circRNAs) originating from various viral families. Notably, these circRNAs have been associated with oncogenesis and alterations in viral fitness. However, identifying their expression has proven more challenging than initially anticipated due to unique viral characteristics. This challenge has the potential to impede progress in our understanding of viral circRNAs. Key hurdles in working with viral genomes include: (1) the presence of repetitive regions that can lead to misalignment of sequencing reads, and (2) unconventional splicing mechanisms that deviate from conserved eukaryotic patterns.To address these challenges, we developed vCircTrappist, a bioinformatic pipeline tailored to identify backsplicing events and pinpoint loci expressing circRNAs in RNA sequencing data. Applying this pipeline, we obtained novel insights from both new and existing datasets encompassing a range of animal and human pathogens belonging to Herpesviridae, Retroviridae, Adenoviridae and Orthomyxoviridae families. Subsequent RT-PCR and Sanger sequencings validated the accuracy of the developed bioinformatic tool for a selection of new candidate viral encoded circRNAs. These findings demonstrate that vCircTrappist is an open and unbiased approach for comprehensive identification of virus-derived circRNAs.Significance StatementCircular RNAs (circRNAs) were revealed to have prominent roles in cellular life in the past decade. They were more recently shown to be expressed by viruses, influencing their infectious cycles and host-pathogen relationship. In this context, viruses that were not previously associated with cellular splicing processes are shown to express circRNAs through unknown mechanisms. These non-canonical circRNAs were already shown to be important in the viral cycle and pathogenesis of the viruses they are encoded from. Here, we propose a bioinformatics pipeline that bypasses the limitations of the existing tools in the identification of viral circRNA. Using this pipeline, we discovered numerous candidates and invite the reader to start its own exploration in the realm of viral encoded circRNAs.Graphical Abstract
Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference
Authors: Feng Ruobing , Champer Jackson 
Published: June 2024

AbstractGene drives have great potential for suppression of pest populations and removal of exotic invasive species. CRISPR homing suppression drive is a powerful but unconfined drive, posing risks of uncontrolled spread. Thus, developing methods for confining a gene drive is of great significance. Tethered drive combines a confined system such as Toxin-Antidote Recessive Embryo (TARE) drive with a strong drive such as a homing suppression drive. It can prevent the homing drive from spreading beyond the confined drive and can be constructed readily, giving it good prospects for future development. However, we have found that care must be taken when deploying tethered drive systems in some scenarios. Simulations of tethered drive in a panmictic population model reveal that successful deployment requires a proper release ratio between the two components, tailored to prevent the suppression drive from eliminating the confined system before it has the chance to spread. Spatial models where the population moves over a one-dimensional landscape display a more serious phenomenon of drive wave interference between the two tethered drive components. If the faster suppression drive wave catches up to the confined drive wave, success is still possible, but it is dependent on drive performance and ecological parameters. Two-dimensional simulations further restrict the parameter range for drive success. Thus, careful consideration must be given to drive performance and ecological conditions, as well as specific release proposals for potential application of tethered drive systems.
Distinct visual processing networks for foveal and peripheral visual fields
Authors: Zhang Jie , Zhou Huihui , Wang Shuo 
Published: June 2024

AbstractFoveal and peripheral vision are two distinct modes of visual processing essential for navigating the world. However, it remains unclear if they engage different neural mechanisms and circuits within the visual attentional system. Here, we trained macaques to perform a free-gaze visual search task using natural face and object stimuli and recorded a large number of 14588 visually responsive neurons from a broadly distributed network of brain regions involved in visual attentional processing. Foveal and peripheral units had substantially different proportions across brain regions and exhibited systematic differences in encoding visual information and visual attention. The spike-LFP coherence of foveal units was more extensively modulated by both attention and visual selectivity, thus indicating differential engagement of the attention and visual coding network compared to peripheral units. Furthermore, we delineated the interaction and coordination between foveal and peripheral processing for spatial attention and saccade selection. Finally, the search became more efficient with increasing target-induced desynchronization, and foveal and peripheral units exhibited different correlations between neural responses and search behavior. Together, the systematic differences between foveal and peripheral processing provide valuable insights into how the brain processes and integrates visual information from different regions of the visual field.Significance StatementThis study investigates the systematic differences between foveal and peripheral vision, two crucial components of visual processing essential for navigating our surroundings. By simultaneously recording from a large number of neurons in the visual attentional neural network, we revealed substantial variations in the proportion and functional characteristics of foveal and peripheral units across different brain regions. We uncovered differential modulation of functional connectivity by attention and visual selectivity, elucidated the intricate interplay between foveal and peripheral processing in spatial attention and saccade selection, and linked neural responses to search behavior. Overall, our study contributes to a deeper understanding of how the brain processes and integrates visual information for active visual behaviors.
Comprehensive evaluation of lifespan-extending molecules inC. elegans
Authors: Phelps Grace B. , Morin Jonas , Pinto Carla , Schoenfeldt Lucas , Guilmot Sebastien , Ocampo Alejandro , Perez Kevin 
Published: June 2024

AbstractThe nematodeC. eleganshas long served as a gold-standard model organism in aging research, particularly since the discovery of long-lived mutants in conserved aging pathways including daf-2 (IGF1) and age-1 (PI3K). Its short lifespan and small size make it highly suitable for high throughput experiments. While numerous molecules have been tested for their effects onC. eleganslifespan, consensus is still lacking regarding the most effective and reproducible compounds. Confounding effects, especially those related to drug-bacteria interactions, remain a contentious issue in the literature. In this study, we evaluated 16 of the most frequently reported lifespan-extending molecules inC. elegans, examining their effects on lifespan with two different diets (live and UV-killed OP50). In addition, we assessed the compounds’ impact on bacterial growth, their effects on various nematode strains, and the impact of the starting age of treatment. Our findings first confirmed robust lifespan extension with many, but not all, of the 16 tested compounds from the literature, and revealed that some of them could be combined to get synergistic effects. Additionally, we showed that some of these compounds also extend lifespan in the flyD. melanogaster,demonstrating a conserved effect across species. Finally, by expanding our screen to a broader pool of molecules, we identified novel lifespan-extending compounds inC. elegans.