bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informing individualized multi-scale neural signatures of clozapine response in patients with treatment-refractory schizophrenia
Authors: Ji Jie Lisa , Lencz Todd , Gallego Juan , Neufeld Nicholas , Voineskos Aristotle , Malhotra Anil , Anticevic Alan 
Published: March 2023

ABSTRACTClozapine is currently the only antipsychotic with demonstrated efficacy in treatment-refractory schizophrenia (TRS). However, response to clozapine differs widely between TRS patients, and there are no available clinical or neural predictive indicators that could be used to increase or accelerate the use of clozapine in patients who stand to benefit. Furthermore, it remains unclear how the neuropharmacology of clozapine contributes to its therapeutic effects. Identifying the mechanisms underlying clozapine’s therapeutic effects across domains of symptomatology could be crucial for development of new optimized therapies for TRS.Here, we present results from a prospective neuroimaging study that quantitatively related heterogeneous patterns of clinical clozapine response to neural functional connectivity at baseline. We show that we can reliably capture specific dimensions of clozapine clinical response by quantifying the full variation across item-level clinical scales, and that these dimensions can be mapped to neural features that are sensitive to clozapine-induced symptom change. Thus, these features may act as “failure modes” that can provide an early indication of treatment (non-)responsiveness. Lastly, we related the response-relevant neural maps to spatial expression profiles of genes coding for receptors implicated in clozapine’s pharmacology, demonstrating that distinct dimensions of clozapine symptom-informed neural features may be associated with specific receptor targets. Collectively, this study informs prognostic neuro-behavioral measures for clozapine as a more optimal treatment for selected patients with TRS. We provide support for the identification of neuro-behavioral targets linked to pharmacological efficacy that can be further developed to inform optimal early treatment decisions in schizophrenia.
Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats
Authors: Steinfeldt Jakob , Wild Benjamin , Buergel Thore , Pietzner Maik , Upmeier zu Belzen Julius , Vauvelle Andre , Hegselmann Stefan , Denaxas Spiros , Hemingway Harry , Langenberg Claudia , Landmesser Ulf , Deanfield John , Eils Roland 
Published: March 2023

AbstractThe COVID-19 pandemic exposed, with few exceptions, a global deficiency in delivering systematic, data-driven guidance to protect citizens and coordinate vaccination programs. At the same time, medical histories are routinely recorded in most healthcare systems and are instantly available for risk assessment. Here, we demonstrate the utility of medical history in determining the risk for 1,883 diseases across clinical specialties and facilitating the rapid response to emerging health threats at the example of COVID-19. We developed a neural network to learn disease-specific risk states from routinely collected health records of 502,460 UK Biobank participants, demonstrating risk stratification for nearly all conditions, and validated this model on 229,830 individuals from the All of US cohort. When integrated into Cox Proportional Hazard Models, we observed significant discriminative improvements over basic demographic predictors for 1,774 (94.3%). After transferring the unmodified risk models to the All of US cohort, the discriminate improvements were replicated for 1,347 (89.8%) of 1,500 investigated endpoints, demonstrating model generalizability across healthcare systems and historically underrepresented groups. We then show that these risk states can be used to identify individuals vulnerable to severe COVID-19 and mortality. Our study demonstrates the currently underused potential of medical history to rapidly respond to emerging health threats by systematically estimating risk for thousands of diseases at once at minimal cost.
Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming
Authors: deCamp Allan C. , Corcoran Martin M. , Fulp William J. , Willis Jordan R. , Cottrell Christopher A. , Bader Daniel L.V. , Kalyuzhniy Oleksandr , Leggat David J. , Cohen Kristen W. , Hyrien Ollivier , Menis Sergey , Finak Greg , Ballweber-Fleming Lamar , Srikanth Abhinaya , Plyler Jason R. , Rahaman Farhad , Lombardo Angela , Philiponis Vincent , Whaley Rachael E. , Seese Aaron , Brand Joshua , Ruppel Alexis M. , Hoyland Wesley , Mahoney Celia R. , Cagigi Alberto , Taylor Alison , Brown David M. , Ambrozak David R. , Sincomb Troy , Mullen Tina-Marie , Maenza Janine , Kolokythas Orpheus , Khati Nadia , Bethony Jeffrey , Roederer Mario , Diemert David , Koup Richard A. , Laufer Dagna S. , McElrath Juliana M. , McDermott Adrian B. , Hedestam Gunilla B. Karlsson , Schief William R. 
Published: March 2023

AbstractVaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.One-Sentence SummaryHuman genetic variation can modulate the strength of vaccine-induced broadly neutralizing antibody precursor B cell responses.
Live-trapping of rodents in urban green spaces across Los Angeles
Authors: Friscia Anthony R. , Helman Sarah , Maloney Molly , Molina-Echavarria Alexandra K. , Nugen Sarah , Punjabi Nihal , Tweedt Isobel , Lynch Jessica W. 
Published: March 2023

AbstractUrban green spaces have the potential to function as multi-benefit spaces, for both human enjoyment and sustaining native wildlife populations. In our study, we trapped for small nocturnal mammals across a series of Los Angeles green spaces. Our results show that native rodents are only present in habitats that support native vegetation; in particular we highlight the native rodent biodiversity on Sage Hill, a coastal sage scrub remnant on the UCLA campus. Other urban parks that are composed of non-native grasses and non-native shrubbery yielded only invasive species of rodents, including Brown Rats (Rattus norvegicus) and House Mice (Mus musculus). Our study points to the ability of renovated green space in Los Angeles to support native fauna. In addition, our study demonstrates some of the difficulties in doing trapping studies in heavily urbanized environments.
Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells
Authors: Verdikt Roxane , Armstrong Abigail A. , Cheng Jenny , Hwang Young Sun , Clark Amander T. , Yang Xia , Allard Patrick 
Published: March 2023

ABSTRACTCannabis, the most consumed illicit psychoactive drug in the world, is increasingly used by pregnant women. However, while cannabinoid receptors are expressed in the early embryo, the impact of phytocannabinoids exposure on early embryonic processes is lacking. Here, we leverage a stepwise in vitro differentiation system that captures early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). We demonstrate that Δ9-THC increases the proliferation of naïve mouse embryonic stem cells (ESCs) but not of their primed counterpart. Surprisingly, this increased proliferation, dependent on the CB1 receptor binding, is only associated with moderate transcriptomic changes. Instead, Δ9-THC capitalizes on ESCs’ metabolic bivalence by increasing their glycolytic rates and anabolic capabilities. A memory of this metabolic rewiring is retained throughout differentiation to Primordial Germ Cell-Like Cells in the absence of direct exposure and is associated with an alteration of their transcriptional profile. These results represent the first in-depth molecular characterization of the impact of Δ9-THC exposure on early stages of germline development.
Successful Modulation of Temporoparietal Junction Activity and Stimulus-Driven Attention by fNIRS-based Neurofeedback – a Randomized Controlled Proof-of-Concept Study
Authors: Kohl Simon H. , Melies Pia , Uttecht Johannes , Lührs Michael , Bell Laura , Mehler David M. A. , Soekadar Surjo R. , Viswanathan Shivakumar , Konrad Kerstin 
Published: March 2023

AbstractThe right temporoparietal junction (rTPJ) is a core hub in neural networks associated with reorienting of attention and social cognition. However, it remains unknown whether participants can learn to actively modulate their rTPJ activity via neurofeedback. Here, we explored the feasibility of functional near-infrared spectroscopy (fNIRS)-based neurofeedback in modulating rTPJ activity and its effect on rTPJ functions such as reorienting of attention and visual perspective taking. In a bidirectional regulation control group design, 50 healthy participants were either reinforced to up- or downregulate rTPJ activation over four days of training.Both groups showed an increase in rTPJ activity right from the beginning of the trainingbut only the upregulation group maintained this effect, while the downregulation group showed a decline from the initial rTPJ activation. This suggests a learning effect in the downregulation exclusively, making it challenging to draw definitive conclusions about the effectiveness of rTPJ upregulation training. However, we observed group-specific effects on the behavioral level. We found a significant group x time interaction effect in the performance of the reorienting of attention task and group-specific changes, with decreased reaction times (RTs) in the upregulation group and increased RTs in the downregulation group across all conditions after the neurofeedback training. Those with low baseline performance showed greater improvements. In the perspective-taking task, however, only time effects were observed that were non-group-specific.These findings demonstrate that fNIRS-based neurofeedback is a feasible method to modulate rTPJ functions with preliminary evidence of neurophysiologically specific effects, thus paving the way for future applications of non-invasive rTPJ modulation in neuropsychiatric disorders.Graphical abstractHighlightsthe right temporoparietal junction (rTPJ) as a core hub for attentive and socio-cognitive functions is a promising target for neuromodulatory interventionsfirst single-blinded, randomized controlled study demonstrates feasibility and effectiveness of the fNIRS-based neurofeedback training of the rTPJ in healthy adultssubjects are able to regulate the rTPJ with different learning characteristicsfirst evidence of a neurophysiologically specific effect on stimulus-driven attentionfindings have important implications for clinical translation of neurofeedback interventions targeting the rTPJ
Lactiplantibacillus plantarumuses ecologically relevant, exogenous quinones for extracellular electron transfer
Authors: Stevens Eric T. , Van Beeck Wannes , Blackburn Benjamin , Tejedor-Sanz Sara , Rasmussen Alycia R. M. , Mevers Emily , Ajo-Franklin Caroline M. , Marco Maria L. 
Published: March 2023

AbstractExtracellular electron transfer (EET) is a metabolic process that frequently uses quinones to couple intracellular redox reactions with extracellular electron acceptors. The physiological relevance of this metabolism for microorganisms that are capable of EET, but unable to synthesize their own quinones, remains to be determined. To address this question, we investigated quinone utilization byLactiplantibacillus plantarum,a microorganism required for food fermentations, performs EET, and is also a quinone auxotroph. L. plantarumselectively used 1,4-dihydroxy-2-naphthoic acid (DHNA), 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ), 1,4-naphthoquinone, and menadione for EET reduction of insoluble iron (ferrihydrite). However, those quinones used for EET also inhibitedL. plantarumgrowth in non-aerated conditions. Transcriptomic analysis showed that DHNA induced oxidative stress inL. plantarumand this was alleviated by the inclusion of an electron acceptor, soluble ferric ammonium citrate (FeAC), in the laboratory culture medium. The presence of DHNA and FeAC during growth also inducedL. plantarumEET metabolism, although activity was still dependent on the presence of exogenous electron shuttles. To determine whether quinone-producing bacteria frequently found together withL. plantarumin food fermentations could be a source of those electron shuttles,L. plantarumEET was measured after incubation withLactococcus lactisandLeuconostoc mesenteroides.Quinone-producingL. lactis,but not a quinone-deficientL. lactisΔmenCmutant, increasedL. plantarumferrihydrite reduction and medium acidification through an EET-dependent mechanism.L. plantarumEET was also stimulated byL. mesenteroides, and this resulted in greater environmental acidification and transient increases inL. plantarumgrowth. Overall, our findings revealed thatL. plantarumovercomes the toxic effects of exogenous quinones to use those compounds, including those made by related bacteria, for EET-conferred, ecological advantages during the early stages of food fermentations.
Cardiopulmonary structural, functional and immune-alterations in a Down syndrome mouse model and upon modulation of EGCG
Authors: Tielemans Birger , Llambrich Sergi , Seldeslachts Laura , Cremer Jonathan , Tsui Hung Chang , Jonckheere Anne-Charlotte , Marain Fopke , Riedel Mirko , Wouters Jens , Herzen Julia , Leszczyński Bartosz , Verbeken Erik , Vanoirbeek Jeroen , Velde Greetje Vande 
Published: March 2023

AbstractIn individuals with Down syndrome (DS), cardiovascular and pulmonary diseases are the most common health problem and result in increased mortality and morbidity. Although these clinical comorbidities are well described, no preclinical models for DS are fully characterized for cardiopulmonary alterations, preventing research to understanding the development and pharmacological modulation of lungs, heart and immune system. Our objective is to characterize the cardiopulmonary and immunological phenotype in Ts65Dn mice and investigate the modulatory effects green tea extract enriched in epigallocatechin 3 gallate (GTE-EGCG). GTE-EGCG administration started at embryonic day 9 and was discontinued at postnatal day (PD) 180. Newborns were longitudinally monitored until PD210 using micro-computed tomography. At endpoint, we characterized the structural, functional and immunological alterations and persistent effects of GTE-EGCG administration. This study revealed normal lung development in the Ts65Dn mice and highlighted RV hypertrophy and immunological alterations. GTE-EGCG administration resulted in genotype-specific and genotype-independent alterations resulting in lung immaturation and airway hyperreactivity. Our results highlight the cardiovascular and immunological phenotype of Ts65Dn mice and potential use for safety studies of therapeutic agents in a DS-specific context.Summary statementThis study longitudinally follows respiratory and cardiac alterations in the Ts65Dn mouse model and describes the impact of prenatal EGCG modulation on the euploid and trisomic phenotype
Behavioral and neuroimaging correlates of attentional biases to angry faces in individuals in remission from depression: a population-derived study
Authors: Nagrodzki Jakub , Passamonti Luca , Schweizer Suzanne , Stretton Jason , Knights Ethan , Henson Richard ,   Cam-CAN, Wolpe Noham 
Published: March 2023

ABSTRACTBackgroundDepressed individuals show attentional biases in the processing of emotional stimuli, such as negative face expressions. Some of these biases persist in previously depressed individuals, but their mechanisms remain largely unknown.MethodsA population-derived cohort (n= 134, 68 females; 21 - 92 years) was recruited by Cam-CAN. Functional MRI was acquired during a gender discrimination task, which used angry and neutral faces. Drift diffusion modelling (DDM) was used to investigate the latent components of the decision process, focusing on the effect of emotional valence. DDM parameters were correlated with activity in brain regions.Results14% of participants reported a history of depression in remission. The best fitting DDM specified a different drift rate for angry and neutral faces. A slower drift rate for angry faces predicted depression in remission (OR 0.092,p= 0.048). This effect persisted after accounting for current depression symptoms and drift rate for neutral faces. Participants with a slower drift rate for angry faces demonstrated increased activations in the bilateral insula, bilateral inferior frontal gyrus and bilateral parietal cortex when viewing angry relative to neutral faces.ConclusionsOur results suggest a persistent attentional bias in the processing of angry faces in individuals with depression in remission, over and above their current depressive symptoms. The imaging findings suggest that the slowing is associated with changes in areas involved in emotional regulation and evidence accumulation. Attentional biases in the processing of emotional information may reflect a trait, rather than state, in individuals with depression.
Delayed postglacial colonization ofBetulain Iceland and the circum North Atlantic
Authors: Harning David J. , Sacco Samuel , Anamthawat-Jónsson Kesara , Ardenghi Nicolò , Thordarson Thor , Raberg Jonathan H. , Sepúlveda Julio , Geirsdóttir Áslaug , Shapiro Beth , Miller Gifford H. 
Published: March 2023

ABSTRACTAs the Arctic continues to warm, woody shrubs are expected to expand northward. This process, known as “shrubification”, has important implications for regional biodiversity, food web structure, and high-latitude temperature amplification. While the future rate of shrubification remains poorly constrained, past records of plant immigration to newly deglaciated landscapes in the Arctic may serve as useful analogues. We provide one new postglacial Holocene sedimentary ancient DNA (sedaDNA) record of vascular plants from Iceland and place a second Iceland postglacialsedaDNA record on an improved geochronology; both show Salicaceae present shortly after deglaciation whereas Betulaceae first appears more than 1000 years later. We find a similar pattern of delayed Betulaceae colonization in eight previously published postglacial sedaDNA records from across the glaciated circum North Atlantic. In nearly all cases, we find that Salicaceae colonizes earlier than Betulaceae and that Betulaceae colonization is increasingly delayed for locations farther from glacial-age woody plant refugia. These trends in Salicaceae and Betulaceae colonization are consistent with the plant families’ environmental tolerances, species diversity, reproductive strategies, seed sizes, and soil preferences. As these reconstructions capture the efficiency of postglacial vascular plant migration during a past period of high-latitude warming, a similarly slow response of some woody shrubs to current warming in glaciated regions, and possibly non-glaciated tundra, may delay Arctic shrubification and future changes in the structure of tundra ecosystems and temperature amplification.
Prostaglandin E2controls the metabolic adaptation of T cells to the intestinal microenvironment
Authors: Villa Matteo , Sanin David E. , Apostolova Petya , Corrado Mauro , Kabat Agnieszka M. , Cristinzio Carmine , Regina Annamaria , Carrizo Gustavo E. , Rana Nisha , Stanczak Michal A. , Baixauli Francesc , Grzes Katarzyna M. , Cupovic Jovana , Solagna Francesca , Hackl Alexandra , Globig Anna-Maria , Hässler Fabian , Puleston Daniel J. , Kelly Beth , Cabezas-Wallscheid Nina , Hasselblatt Peter , Bengsch Bertram , Zeiser Robert , Sagar  , Buescher Joerg M. , Pearce Edward J , Pearce Erika L. 
Published: March 2023

AbstractImmune cells must adapt to different environments during the course of an immune response. We studied the adaptation of CD8+T cells to the intestinal microenvironment and how this process shapes their residency in the gut. CD8+T cells progressively remodel their transcriptome and surface phenotype as they acquire gut residency, and downregulate expression of mitochondrial genes. Human and mouse gut-resident CD8+T cells have reduced mitochondrial mass, but maintain a viable energy balance to sustain their function. We found that the intestinal microenvironment is rich in prostaglandin E2(PGE2), which drives mitochondrial depolarization in CD8+T cells. Consequently, these cells engage autophagy to clear depolarized mitochondria, and enhance glutathione synthesis to scavenge reactive oxygen species (ROS) that result from mitochondrial depolarization. Impairing PGE2sensing promotes CD8+T cell accumulation in the gut, while tampering with autophagy and glutathione negatively impacts the T cell population. Thus, a PGE2-autophagy-glutathione axis defines the metabolic adaptation of CD8+T cells to the intestinal microenvironment, to ultimately influence the T cell pool.
Fast Approximate IsoRank for Scalable Global Alignment of Biological Networks
Authors: Devkota Kapil , Blumer Anselm , Cowen Lenore , Hu Xiaozhe 
Published: March 2023

AbstractA well-studied approximate version of the graph matching problem is directly relevant for the study of protein-protein interaction networks. Called by the computational biology community Global Network Alignment, the two networks to be matched are derived from the protein-protein interaction (PPI) networks from organisms of two different species. If these two species evolved recently from a common ancestor, we can view the two PPI networks as a single network that evolved over time. It is the two versions of this network that we want to align using approximate graph matching. The first spectral method for the PPI global alignment problem proposed by the biological community was the IsoRank method of Singh et al. This method for global biological network alignment is still used today. However, with the advent of many more experiments, the size of the networks available to match has grown considerably, making running IsoRank unfeasible on these networks without access to state of the art computational resources. In this paper, we develop a new IsoRank approximation, which exploits the mathematical properties of IsoRank’s linear system to solve the problem in quadratic time with respect to the maximum size of the two PPI networks. We further propose a computationally cheaper refinement to this initial approximation so that the updated result is even closer to the original IsoRank formulation. In experiments on synthetic and real PPI networks, we find that the results of our approximate IsoRank are not only nearly as accurate as the original IsoRank results but are also much faster, which makes the global alignment of large-scale biological networks feasible and scalable.