bluuebunny/crossref_metadata_2025_split huggingface dataset:
IP10 levels refine severity prognostication in COVID-19 and implicate causes of clinical deterioration: lessons for pandemic preparedness
Authors: Das Abhishek , Wei Jia , McKenzie Duncan , Snell Luke , Sasidharan Shruthi , Vantourout Pierre , Zlatareva Iva , Merrick Blair , Thomas Benjamin , Adiga Vasista , Hussain Khiyam , Batra Rahul , Davies Daniel , Su Jia , Bisnauthsing Karen , Martinez Lauren , Ahmed Asma , Bindhu Hima , Chetan Nirutha , Macrina Maria , Tripathi Himanshu , O’Hara Geraldine , Fairhead Cassandra , Drazdauskaite Gabija , Lock Helen , Dias Mary , Ibrahim Mohammad A. A. , Hayday Thomas , D’Souza George , Edgeworth Jonathan , Vyakarnam Annapurna , Pouwels Koen B , Hayday Adrian C. 
Published: June 2024

SummaryBackgroundEmerging pandemics place immense strains on healthcare systems that may be ameliorated by rapid development of biomarkers whose measurements may predict disease severity and additionally inform about disease causation. Conspicuously, such routine measures rarely include immunological cytokines or chemokines, despite their contributions to host protection and immunopathology.MethodsMultiplex bead-array and ELISA-based serum cytokine and chemokine measurements, routinely employed clinical laboratory measures, and clinical outcomes were collectively fed into predictive model development for prognostication of COVID-19 severity in an unvaccinated UK cohort (Discovery; early-to-mid 2020), with subsequent external validation among a pauci-vaccinated UK cohort (early 2021) and part-vaccinated India cohort (early 2022 to early 2023). Correlates of disease severity were assessed by high-content spectral flow cytometry.FindingsIncorporating a practical test for the chemokine IP10 (a.k.a. CXCL10) alongside routine clinical laboratory assays increased at-admission test accuracy to prognosticate intensive care requirements or in-hospital mortality at 30 days in the Discovery and Validation cohorts. In the India cohort, high IP10 levels predicted terminal deterioration among unvaccinated persons. High-resolution immune-profiling within subsets of the Discovery and India cohorts associated a T cell-centric signature with disease severity and with high IP10 levels, thereby identifying candidate drivers of COVID-19 deterioration.ConclusionsIP10 levels measured at or around hospital admission offer a practical biomarker enhancing COVID-19 patient outcome prognostication, particluarly in unvaccinated individuals, and offer mechanistic insights into pathogenesis. Thus, prompt application of systems immune-profiling in future pandemics might rapidly identify prognostic and mechanistic biomarkers of patient deterioration, aiding clinical decision-making at a time of severe healthcare strain.FundingMedical Research Council grant, CARDINNATE.
Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease
Authors: Zeng Xuemei , Lafferty Tara K. , Sehrawat Anuradha , Chen Yijun , Ferreira Pamela C. L. , Bellaver Bruna , Povala Guilherme , Kamboh M. Ilyas , Klunk William E. , Cohen Ann D. , Lopez Oscar L. , Ikonomovic Milos D. , Pascoal Tharick A. , Ganguli Mary , Villemagne Victor L. , Snitz Beth E. , Karikari Thomas K. 
Published: June 2024

AbstractBackgroundBlood-based biomarkers are gaining grounds for Alzheimer’s disease (AD) detection. However, two key obstacles need to be addressed: the lack of methods for multi-analyte assessments and the need for markers of neuroinflammation, vascular, and synaptic dysfunction. Here, we evaluated a novel multi-analyte biomarker platform, NULISAseq CNS disease panel, a multiplex NUcleic acid-linked Immuno-Sandwich Assay (NULISA) targeting ∼120 analytes, including classical AD biomarkers and key proteins defining various disease hallmarks.MethodsThe NULISAseq panel was applied to 176 plasma samples from the MYHAT-NI cohort of cognitively normal participants from an economically underserved region in Western Pennsylvania. Classical AD biomarkers, including p-tau181, p-tau217, p-tau231, GFAP, NEFL, Aβ40, and Aβ42, were also measured using Single Molecule Array (Simoa). Amyloid pathology, tau pathology, and neurodegeneration were evaluated with [11C] PiB PET, [18F]AV-1451 PET, and MRI, respectively. Linear mixed models were used to examine cross-sectional and Wilcoxon rank sum tests for longitudinal associations between NULISA biomarkers and AD pathologies. Spearman correlations were used to compare NULISA and Simoa.ResultsNULISA concurrently measured 116 plasma biomarkers with good technical performance, and good correlation with Simoa measures. Cross-sectionally, p-tau217 was the top hit to identify Aβ pathology, with age, sex, andAPOEgenotype-adjusted AUC of 0.930 (95%CI: 0.878-0.983). Fourteen markers were significantly decreased in Aβ-PET+ participants, including TIMP3, which regulates brain Aβ production, the neurotrophic factor BDNF, the energy metabolism marker MDH1, and several cytokines. Longitudinally, FGF2, IL4, and IL9 exhibited Aβ PET-dependent yearly increases in Aβ-PET+ participants. Markers with tau PET-dependent longitudinal changes included the microglial activation marker CHIT1, the reactive astrogliosis marker CHI3L1, the synaptic protein NPTX1, and the cerebrovascular markers PGF, PDGFRB, and VEFGA; all previously linked to AD but only reliably measured in cerebrospinal fluid. SQSTM1, the autophagosome cargo protein, exhibited a significant association with neurodegeneration status after adjusting age, sex, andAPOEε4 genotype.ConclusionsTogether, our results demonstrate the feasibility and potential of immunoassay-based multiplexing to provide a comprehensive view of AD-associated proteomic changes. Further validation of the identified inflammation, synaptic, and vascular markers will be important for establishing disease state markers in asymptomatic AD.
Factors Associated with the Frequency of Medical Consultations in 1,355,354 Patients with Various Types of Diabetes Mellitus
Authors: Vera-Ponce Víctor Juan , Loayza-Castro Joan A. , Tapia-Limonchi Rafael , Vigil-Ventura Enrique 
Published: June 2024

AbstractIntroductionProper management of diabetes mellitus (DM) is essential to prevent long-term complications, improve patients’ quality of life, and reduce the economic burden on healthcare services.ObjectiveTo determine the factors associated with the number of medical consultations received in the last quarter by patients with different types of diabetes affiliated with the Comprehensive Health Insurance (SIS: acronym in Spanish) in Peru.MethodsA cross-sectional analysis of the database of patients with DM affiliated with SIS in Peru was conducted. Two robust variance regression models were used to identify potential associated factors.ResultsData from 1,355,354 patients were analyzed. In model 1, which included comorbidities as separate variables, it was found that men, older individuals (especially those aged 60-69), and residents of the jungle region had a higher probability of receiving more medical consultations. The presence of obesity/dyslipidemia, hypertension, and mental health disorders also increased the likelihood of more consultations. In comparison, patients with type 2 DM had fewer consultations compared to those with type 1 DM. The findings were consistent with the first model in model 2, which included the total number of comorbidities instead of each separately. Additionally, a higher total number of comorbidities was associated with an increased number of medical consultations.ConclusionsSeveral vital factors influencing the frequency of medical consultations received by DM patients have been identified. Adapting healthcare services to address regional disparities in access to and use of medical services is crucial.
MUTATE: A Human Genetic Atlas of Multi-organ AI Endophenotypes using GWAS Summary Statistics
Authors: Boquet-Pujadas Aleix , Zeng Jian , Tian Ye Ella , Yang Zhijian , Shen Li , Zalesky Andrew , Davatzikos Christos ,   the MULTI consortium, Wen Junhao 
Published: June 2024

AbstractArtificial intelligence (AI) has been increasingly integrated into imaging genetics to provide intermediate phenotypes (i.e., endophenotypes) that bridge the genetics and clinical manifestations of human disease. However, the genetic architecture of these AI endophenotypes remains largely unexplored in the context of human multi-organ system diseases. Using publicly available GWAS summary statistics from the UK Biobank, FinnGen, and the Psychiatric Genomics Consortium, we comprehensively depicted the genetic architecture of 2024 multi-organ AI endophenotypes (MAEs). We comparatively assessed the SNP-based heritability, polygenicity, and natural selection signatures of 2024 MAEs using methods commonly used in the field. Genetic correlation and Mendelian randomization analyses reveal both within-organ relationships and cross-organ interconnections. Bi-directional causal relationships were established between chronic human diseases and MAEs across multiple organ systems, including Alzheimer’s disease for the brain, diabetes for the metabolic system, asthma for the pulmonary system, and hypertension for the cardiovascular system. Finally, we derived polygenic risk scores for the 2024 MAEs for individuals not used to calculate MAEs and returned these to the UK Biobank. Our findings underscore the promise of the MAEs as new instruments to ameliorate overall human health. All results are encapsulated into the MUTATE genetic atlas and are publicly available athttps://labs-laboratory.com/mutate.
Synchronous seasonal plasticity in colouration, behaviour, and visual gene expression in a wild butterfly population
Authors: Hirzel Grace E. , Brady Noah K. , Reed Robert D. , Westerman Erica L. 
Published: June 2024

AbstractPhenotypic plasticity allows many animals to quickly respond to seasonal changes in their environment. Seasonal changes to physiological systems, such as sensory systems, may explain other more obvious changes in behaviour, often working synergistically with changes in morphology. Here we investigate if there are covarying seasonal changes to morphology, behaviour, and the visual system in the seasonally plastic butterflyJunonia coenia. To describe when seasonal wing patterns occur at our field sites in the central United States and for analysis of gene expression in eye tissue, we collected animals throughout the summer and fall in 2018, 2019, 2020, and 2021. For the first three years we also visited field sites to observe behaviour during focal watches and point counts throughout the flight period. We found that moreJ. coeniaexhibit seasonal dark wing patterns in September and October compared to butterflies collected in previous months. This change in wing pattern correlates to an increase in basking behaviour. Eye tissues of dark fall animals and lighter summer animals exhibit different patterns of gene expression, including clock genes and genes involved in eye pigment synthesis. Subsequent analysis of monthly variation in opsin gene expression in eye tissues confirmed that opsin genes are not differentially expressed throughout the year, thoughperiodgene expression is higher in the fall, and females have higher blue opsin gene expression than males. This concurrent seasonal shift in colouration, behaviour, and underlying visual physiology indicates thatJ. coeniaundergoes a complex shift in phenotype that encompasses more than simple changes to thermoregulation.
Contagious vocal reaction forms avian vocal exchange: an experimental study in Java sparrows
Authors: Kikuchi Sota , Kondo Noriko , Koda Hiroki 
Published: June 2024

AbstractVocal exchange or turn-taking - an interaction in which vocalizer alternation occurs at very short intervals to avoid overlapping vocalizations - occurs not only in human conversation but also in animal communications, characterized by temporal regularities in the timing of spontaneous and response vocalizations. This temporal regularity has been observed in social mammals or primates, including humans, but little has been known about vocal exchange of call in birds, a highly vocal animal. Here, we experimentally manipulated a face-to-face setting with Java sparrows to observe their vocal exchange between two birds and analyzed its temporal regularity. The results showed that the temporal regularity of their vocal exchange was significantly different from that of primates. In particular, Java sparrows responded reflexively to the vocalizations of other individuals, but they showed no tendency to await the vocalizations of other individuals. Similar to behavioral synchrony, which is commonly observed in avian species, contagious vocalization possibly shapes avian vocal exchange. These results suggested the need for careful comparative studies of vocal exchange among social animals, considering the differences in the ecological backgrounds of group formation.
Pathogen genomic surveillance as a scalable framework for precision phage therapy
Authors: Koncz Mihály , Stirling Tamás , Mehdi Hiba Hadj , Méhi Orsolya , Eszenyi Bálint , Asbóth András , Apjok Gábor , Tóth Ákos , Orosz László , Vásárhelyi Bálint Márk , Ari Eszter , Daruka Lejla , Polgár Tamás Ferenc , Schneider György , Zalokh Sif Aldin , Számel Mónika , Fekete Gergely , Bohár Balázs , Varga Karolina Nagy , Visnyovszki Ádám , Székely Edit , Licker Monica-Sorina , Izmendi Oana , Costache Carmen , Gajic Ina , Lukovic Bojana , Molnár Szabolcs , Szőcs-Gazdi Uzonka Orsolya , Bozai Csilla , Indreas Marina , Kristóf Katalin , Van der Henst Charles , Breine Anke , Pál Csaba , Papp Balázs , Kintses Bálint 
Published: June 2024

AbstractPhage therapy is gaining increasing interest in the fight against critically resistant nosocomial pathogens. However, the narrow host range of bacteriophages hampers the development of broadly effective phage therapeutics and demands precision approaches. Here we combine large-scale phylogeographical analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistantAcinetobacter baumannii,a top-priority pathogen. Our analysis reveals that a few strain types dominate infections in each world region, with their geographical distribution remaining stable within six years. As we demonstrate in Eastern Europe, this spatio-temporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of a four-phage cocktail against the most prevalent strain type in bothin vitroandin vivoanimal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy.HighlightsA few carbapenem-resistantAcinetobacter baumanniitypes dominate infections worldwidePhylogeography reveals stable strain composition of individual countries over a six-year periodThis spatio-temporal distribution allows preemptive preparation of region-specific phage collectionsA four-phage cocktail is efficacious against the most prevalent strain type in Europe.
Deciphering the molecular landscape of human peripheral nerves: implications for diabetic peripheral neuropathy
Authors: Ferreira Diana Tavares , Shen Breanna Q , Mwirigi Juliet M , Shiers Stephanie , Sankaranarayanan Ishwarya , Kotamarti Miriam , Inturi Nikhil N , Mazhar Khadijah , Ubogu Eroboghene E , Thomas Geneva , Lalli Trapper , Wukich Dane , Price Theodore J 
Published: June 2024

ABSTRACTDiabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus that is caused by metabolic toxicity to peripheral axons. We aimed to gain deep mechanistic insight into the disease process using bulk and spatial RNA sequencing on tibial and sural nerves recovered from lower leg amputations in a mostly diabetic population. First, our approach comparing mixed sensory and motor tibial and purely sensory sural nerves shows key pathway differences in affected nerves, with distinct immunological features observed in sural nerves. Second, spatial transcriptomics analysis of sural nerves reveals substantial shifts in endothelial and immune cell types associated with severe axonal loss. We also find clear evidence of neuronal gene transcript changes, likePRPH,in nerves with axonal loss suggesting perturbed RNA transport into distal sensory axons. This motivated further investigation into neuronal mRNA localization in peripheral nerve axons generating clear evidence of robust localization of mRNAs such asSCN9AandTRPV1in human sensory axons. Our work gives new insight into the altered cellular and transcriptomic profiles in human nerves in DPN and highlights the importance of sensory axon mRNA transport as an unappreciated potential contributor to peripheral nerve degeneration.
Age-related changes in Higuchi’s fractal dimension in healthy human EEG are anti-correlated with changes in oscillatory power and 1/f slope
Authors: Aggarwal Srishty , Ray Supratim 
Published: June 2024

AbstractNon-linear dynamical methods such as Higuchi’s fractal dimension (HFD) are often used to study the complexities of brain activity. In human electroencephalogram (EEG), while power in the gamma band (30-70 Hz) and the slope of the power spectral density (PSD) have been shown to reduce with healthy aging, there are conflicting findings regarding how HFD and other measures of complexity vary with aging. Further, the dependence of HFD on features obtained from PSD (such as gamma power and slope) has not been thoroughly probed. To address these issues, we computed time and frequency resolved HFD for EEG data collected from elderly population (N=217), aged between 50-88 years, for baseline (BL) eyes open state and during a fixation task in which visual grating stimuli that induce strong gamma oscillations were presented. During BL, HFD increased with age at frequencies upto 150 Hz, but surprisingly showed an opposite trend at higher frequencies. Interestingly, this change in HFD was opposite to the age-related change in PSD 1/f slope. Further, stimulus-related changes in HFD were anti-correlated with the changes in oscillatory power. However, age classification using HFD was slightly better than classification using spectral features (power and slope). Therefore, HFD could effectively integrate various spectral features as well as some non-linearities not captured using spectral analysis, which could enhance our understanding of brain dynamics underlying healthy aging.Significance StatementHiguchi’s fractal dimension (HFD) is used widely to understand the complexity and non-linearities in brain signals. Previous studies have found inconsistent results regarding the change of HFD with aging. We tested whether this could be due to changes in spectral measures like oscillatory power and slope with aging by computing time-frequency resolved HFD for EEG data from elderly subjects (N=217; 50-88 years). We found that HFD increased with age upto 150 Hz, but decreased at higher frequencies. Interestingly, age-related changes in HFD were negatively correlated to the corresponding changes in slope and oscillatory power. Age classification using HFD was slightly better than spectral features, suggesting that HFD effectively integrates spectral as well as non-linear changes in brain signals with aging.
“Parvalbumin interneuron activity induces slow cerebrovascular fluctuations in awake mice”
Authors: Rakymzhan Adiya , Fukuda Mitsuhiro , Kozai Takashi Daniel Yoshida , Vazquez Alberto Luis 
Published: June 2024

AbstractNeuronal regulation of cerebrovasculature underlies brain imaging techniques reliant on cerebral blood flow (CBF) changes. However, interpreting these signals requires understanding their neural correlates. Parvalbumin (PV) interneurons are crucial in network activity, but their impact on CBF is not fully understood. Optogenetic studies show that stimulating cortical PV interneurons induces diverse CBF responses, including rapid increases, decreases, and slower delayed increases. To clarify this relationship, we measured hemodynamic and neural responses to optogenetic stimulation of PV interneurons expressing Channelrhodopsin-2 during evoked and ongoing resting-state activity in the somatosensory cortex of awake mice. Two-photon microscopy (2P) Ca2+ imaging showed robust activation of PV-positive (PV+) cells and inhibition of PV-negative (PV-) cells. Prolonged PV+ cell stimulation led to a delayed, slow CBF increase, resembling a secondary peak in the CBF response to whisker stimulation. 2P vessel diameter measurements revealed that PV+ cell stimulation induced rapid arterial vasodilation in superficial layers and delayed vasodilation in deeper layers. Ongoing activity recordings indicated that both PV+ and PV-cell populations modulate arterial fluctuations at rest, with PV+ cells having a greater impact. These findings show that PV interneurons generate a complex depth-dependent vascular response, dominated by slow vascular changes in deeper layers.
The value of initiating a pursuit in temporal decision-making
Authors: Sutlief Elissa , Walters Charlie , Marton Tanya , Hussain Shuler Marshall G 
Published: June 2024

AbstractReward-rate maximization is a prominent normative principle commonly held in behavioral ecology, neuroscience, economics, and artificial intelligence. Here, we identify and compare equations for evaluating the worth of initiating pursuits that an agent could implement to enable reward-rate maximization. We identify two fundamental temporal decision-making categories requiring the valuation of the initiation of a pursuit—forgo and choice decision-making—over which we generalize and analyze the optimal solution for how to evaluate a pursuit in order to maximize reward rate. From this reward-rate-maximizing formulation, we derive expressions for the subjective value of a pursuit, i.e. that pursuit’s equivalent immediate reward magnitude, and reveal that time’s cost is composed of anapportionment, in addition to, anopportunitycost. By re-expressing subjective value as a temporal discounting function, we show precisely how the temporal discounting function of a reward-rate-optimal agent is sensitive not just to the properties of a considered pursuit, but to the time spent and reward acquired outside of the pursuit for every instance spent within it. In doing so, we demonstrate how the apparent discounting function of a reward-rate-optimizing agent depends on the temporal structure of the environment and is a combination of hyperbolic and linear components, whose contributions relate the apportionment and opportunity cost of time, respectively. We further then show how purported signs of suboptimal behavior (hyperbolic discounting, the Delay effect, the Magnitude effect, the Sign effect) are in fact consistent with reward-rate maximization. Having clarified what features are andare notsigns of optimal decision-making, we analyze the impact of the misestimation of reward rate-maximizing parameters in order to better account for the pattern of errors actually observed in humans and animals. We find that error in agents’ assessment of the apportionment of time that underweights the time spent outside versus inside a considered pursuit type is the likely driver of suboptimal temporal decision-making observed behaviorally. We term this the Malapportionment Hypothesis. This generalized form for reward-rate maximization and its relation to subjective value and temporal discounting allows the true pattern of errors exhibited by humans and animals to be more deeply understood, identified, and quantified, which is key to deducing the learning algorithms and representational architectures actually used by humans and animals to evaluate the worth of pursuits.