bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finding the best cell lines across pan-cancer to use in pre-clinical research as a proxy for patient tumor samples considering immune cells, multi-omics, and cancer pathways
Authors: Bose Banabithi , Bozdag Serdar 
Published: December 2022

AbstractIn pre-clinical trials of anti-cancer drugs, cell lines are utilized as a model for patient tumor samples to understand the response of drugs. However,in vitroculture of cell lines, in general, alters the biology of the cell lines and likely gives rise to systematic differences from the tumor samples’ genomic profiles; hence the drug response of cell lines may deviate from actual patients’ drug response. In this study, we computed a similarity score for the selection of cell lines depicting the close and far resemblance to patient tumor samples in twenty-two different cancer types at genetic, genomic, and epigenetic levels integrating multi-omics datasets. We also considered the presence of immune cells in tumor samples and cancer-related biological pathways in this score which aids personalized medicine research in cancer. We showed that based on these similarity scores cell lines were able to recapitulate the drug response of patient tumor samples for several FDA-approved cancer drugs in multiple cancer types. Based on these scores, several of the high-rank cell lines were shown to have a close likeness to the corresponding tumor type in previously reported in vitro experiments.
A Unified Filtering Method for Estimating Asymmetric Orientation Distribution Functions: Where and How Asymmetry Occurs in the Brain
Authors: Poirier Charles , Descoteaux Maxime 
Published: December 2022

AbstractNumerous filtering methods have been proposed for estimating asymmetric orientation distribution functions (ODFs) for diffusion magnetic resonance imaging (dMRI). It can be hard to make sense of all these different methods, which share similar features and result in similar outputs. The objectives of this work are two-fold: to disentangle the various filtering methods proposed in the past for estimating asymmetric ODFs, and to study the occurrence of asymmetric patterns in dMRI brain acquisitions. Hence, we describe a new filtering equation for estimating asymmetric ODFs resulting from the unification of these previously proposed filtering methods. Our method is distributed as an open-source GPU-accelerated python software to facilitate its integration into any existing dMRI processing pipeline. Following its validation on toy datasets, we apply our method to multi-shell multi-tissue fiber ODF reconstructions for 21 subjects from the Human Connectome Project in test-retest acquisitions. Our results show that our method estimates branching, fanning, bending, ending and other complex asymmetric fiber configurations in less than 2 minutes. Also, our novel number of fiber directions (NuFiD) index reveals that the filtering reduces the number of peak directions in the resulting asymmetric representation. Finally, our MNI-aligned template of asymmetries, describing the degree of asymmetry of each voxel, suggests that at least 60% of brain voxels in a dMRI acquisition contain asymmetric fiber configurations.
Persistent spectral theory-guided protein engineering
Authors: Qiu Yuchi , Wei Guo-Wei 
Published: December 2022

AbstractWhile protein engineering, which iteratively optimizes protein fitness by screening the gigantic mutational space, is constrained by experimental capacity, various machine learning models have substantially expedited protein engineering. Three-dimensional protein structures promise further advantages, but their intricate geometric complexity hinders their applications in deep mutational screening. Persistent homology, an established algebraic topology tool for protein structural complexity reduction, fails to capture the homotopic shape evolution during the filtration of a given data. This work introduces aTopology-offeredproteinFitness (TopFit) framework to complement protein sequence and structure embeddings. Equipped with an ensemble regression strategy, TopFit integrates the persistent spectral theory, a new topological Laplacian, and two auxiliary sequence embeddings to capture mutation-induced topological invariant, shape evolution, and sequence disparity in the protein fitness landscape. The performance of TopFit is assessed by 34 benchmark datasets with 128,634 variants, involving a vast variety of protein structure acquisition modalities and training set size variations.
Homeostasis, injury and recovery dynamics at multiple scales in a self-organizing intestinal crypt
Authors: Gall Louis , Duckworth Carrie , Jardi Ferran , Lammens Lieve , Parker Aimée , Bianco Ambra , Kimko Holly , Pritchard D. Mark , Pin Carmen 
Published: December 2022

AbstractWe have built a multi-scale agent-based model (ABM) that reproduces the self-organizing behaviour reported for the intestinal crypt. We demonstrate that a stable spatial organization emerges from the dynamic interaction of multiple signalling pathways, such as Wnt, Notch, BMP, RNF43/ZNRF3 and YAP-Hippo pathways, which regulate proliferation and differentiation, respond to environmental mechanical cues, form feedback mechanisms and modulate the dynamics of the cell cycle protein network.The model recapitulates the crypt phenotype reported after persistent stem cell ablation and after the inhibition of the CDK1 cycle protein. Moreover, we simulated 5-fluorouracil (5-FU)-induced toxicity at multiple scales starting from DNA and RNA damage, which disturbs the cell cycle, cell signalling, proliferation, differentiation and migration and leads to loss of barrier integrity. During recovery, our in-silico crypt regenerates its structure in a self-organizing, dynamic fashion driven by dedifferentiation and enhanced by negative feedback loops.Overall, we present a systems model able to simulate the disruption of molecular events and its impact across multiple levels of epithelial organization and demonstrate its application to epithelial research and drug discovery.
Pre-Injury Mechanoreceptor Ablation Reduces Nociceptor-Driven Spinal Cord Injury-Induced Neuropathic Pain
Authors: Sliwinski Christopher , Heutehaus Laura , Taberner Francisco J. , Weiss Lisa , Kampanis Vasileios , Tolou-Dabbaghian Bahardokht , Cheng Xing , Motsch Melanie , Heppenstall Paul A. , Kuner Rohini , Franz Steffen , Lechner Stefan G. , Weidner Norbert , Puttagunta Radhika 
Published: December 2022

ABSTRACTEvidence from previous studies supports the concept that spinal cord injury (SCI) induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree nociceptors and mechanoreceptors contribute. Sensorimotor activation-based interventions (e.g. treadmill training) have been shown to reduce NP following experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. At the same time, nociceptors have been shown to become hyperexcitable early after SCI and peptidergic axons sprout into deeper laminae of the below injury level dorsal horn. The aim of the present study is to comprehensively understand the relative contribution of each pathway in respect to NP presentation in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B (TrkB) expressing mechanoreceptorsbefore SCImechanical allodynia was reduced. The identical genetic ablationafter SCIdid not yield any change in pain behavior. CGRP sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. Moreover, detection of hyperexcitability in nociceptors, not in mechanoreceptors, in skin-nerve preparations of contusion SCI mice 7 days after injury makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. SNS reporter mice allowing specific visualization of the entire nociceptor population confirmed significant sprouting of respective neurons into laminae III/IV as early as 5 days post-injury. Genetic ablation of SNS-Cre mice severely affected their overall health condition, which precluded them to undergo experimental SCI and subsequent further analysis. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors with consecutive peptidergic fiber sprouting in the dorsal horn are confirmed as the likely main driver of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.
Uncovering directional epistasis in bi-parental populations using genomic data
Authors: Rio Simon , Charcosset Alain , Moreau Laurence , Mary-Huard Tristan 
Published: December 2022

AbstractEpistasis, commonly defined as interaction effects between alleles of different loci, is an important genetic component of the variation of phenotypic traits in natural and breeding populations. In addition to its impact on variance, epistasis can also affect the expected performance of a population and is then referred to as directional epistasis. Before the advent of genomic data, the existence of epistasis (both directional and non-directional) was investigated based on complex and expensive mating schemes involving several generations evaluated for a trait of interest. In this study, we propose a methodology to detect the presence of epistasis based on simple inbred bi-parental populations, both genotyped and phenotyped, ideally along with their parents. Thanks to genomic data, parental proportions as well as shared parental proportions between inbred individuals can be estimated. They allow the evaluation of epistasis through a test of the expected performance for directional epistasis or the variance of genetic values. This methodology was applied to two large multi-parental populations, i.e., the American maize and soybean nested association mapping populations, evaluated for different traits. Results showed significant epistasis, especially for the test of directional epistasis, e.g., the increase in anthesis to silking interval observed in most maize inbred progenies or the decrease in grain yield observed in several soybean inbred progenies. In general, the effects detected suggested that shuffling allelic assocations of both elite parents had a detrimental effect on the performance of their progeny. This methodology is implemented in the EpiTest R-package and can be applied to any bi-/multi-parental inbred population evaluated for a trait of interest.
Investigation of a mathematical model describing global cancer growth and treatment: An inhomogeneous model based on the generalized logistic equation
Authors: Wang Haofan , Mao Yitao , Zhang Zhen , Xu Zhenxiong , Luo Shuyang , Li Weifeng , Zou Sibin , Chen Bin , Wen Huiquan , Lin Longxin , Liao Weihua , Huang Mingsheng 
Published: December 2022

SummaryTumor growth is manifestation of the evolution of a complex system. Researchers have limited scope of modelling studies on specific aspects or stages of the process. It has led to unsatisfactory explanation of clinical observations. We hereby demonstrated that an inhomogeneous model built on the generalized logistic equation could serve better. It was developed to describe the whole process of tumor progression, clinically observed independence of index tumor growth from spread of the disease and growth deceleration during early stage of solid tumors. It was validated by simulating the coexistence of exponential and sigmoidal growth in chronic lymphocytic leukaemia, theories of tumor heterogeneity, as well as by accommodating notions pertaining to tumor treatment and prognosis. We thought therefore it was an interesting and not unjustifiable description of actual tumor growth in human body and hoped it might encourage more researchers to look at tumor modelling from a clinical perspective.
Relationship between the concentration of ergothioneine in plasma and the likelihood of developing pre-eclampsia
Authors: Kenny Louise C. , Brown Leslie W , Ortea Paloma , Tuytten Robin , Kell Douglas B. 
Published: December 2022

AbstractErgothioneine, an antioxidant nutraceutical mainly at present derived from the dietary intake of mushrooms, has been suggested as a preventive for pre-eclampsia. We analysed early pregnancy samples for a cohort of 432 first time mothers as part of the Screening for Endpoints in Pregnancy (SCOPE, European branch) project to determine the concentration of ergothioneine in their plasma. There was a weak association between the ergothioneine levels and maternal age, but none for BMI. Of these 432 women, 97 went on to develop pre-term (23) or term (74) pre-eclampsia. If a threshold was set at the 90thpercentile of the reference range in the control population (≥ 462 ng/mL), only one of these 97 women (1%) developed pre-eclampsia, versus 97/432 (22.5%) whose ergothioneine level was below this threshold. One possible interpretation of these findings, consistent with previous experiments in a reduced uterine perfusion model in rats, is that ergothioneine may indeed prove protective against pre-eclampsia in humans. An intervention study of some kind now seems warranted.
Temporal DCE Profile of Brain Metastasis with A Comparison of Pseudoprogression Cases
Authors: Turk Sevcan , Kurokawa Ryo , Naganawa Shotaro , Wallace Jacob , Ma Tianwen , Johnson Timothy , Moritani Toshio , Kim John 
Published: December 2022

AbstractPurposeTo demonstrate Dynamic Contrast-Enhanced (DCE) perfusion changes in brain metastasis patients after chemoradiation therapy within the treatment responders (true-response group and pseudoprogression group) and between the true-response and pseudoprogression groups.Materials and Methods38 true-response patients with 38 brain metastases (13 melanoma, 11 lung, 7 breast, 7 others) with 3 consecutive DCE-MRI examinations (pretreatment, first follow-up and second follow-up) and 7 pseudoprogression patients with 10 melanoma metastases with 2 consecutive DCE-MRI examinations (pretreatment, first follow-up) were evaluated. DCE-MRI parameters and permeability graphs increase (rapid, slow, medium) and course pattern (washout, plateau, persistent) were analyzed and compared between the timing of the examinations and between the true-response and pseudoprogression groups, using paired t-tests and Mann-Whitney U-tests as appropriate. Automatic assessment of washout curves by Olea Brain Software was reviewed.ResultsPretreatment mean wash-in (15.3±24.7 vs 6.50±14.2, P<0.02), Vp (0.13±0.17 vs 0.06±0.06, P<0.01), Ktrans (0.37±0.48 vs 0.16±0.18, P<0.01), peak enhancement (123±98 vs 76±60.5, P<0.01), AUC (14×104±18×104vs 5×104±10×104, P<0.001) values were significantly higher than that of post-treatment. Other DCE metrics and permeability graph factors between pre-and post-treatment MRI were not significantly different. There was no statistically significant difference in any imaging factors in pre-or first post-treatment DCE-MRI examinations between the true-response and pseudoprogression groups.ConclusionWash-in, Vp, Ktrans, peak enhancement, AUC values in DCE perfusion were significantly decreased after chemoradiation therapy in the responders. No statistically significant difference was shown between the true-response and pseudoprogression groups on either pre-or post-treatment, indicating the homogeneous permeability profiles in the responders.
Using Twitter Data Analysis to Understand the Perceptions, Awareness, and Barriers to the Wide Use of Pre-Exposure Prophylaxis in the United States
Authors: Erdengasileng Arslan , Tian Shubo , Green Sara S. , Naar Sylvie , He Zhe 
Published: December 2022

AbstractUser-generated social media posts such as tweets can provide insights about the public’s perception, cognitive, and behavioral responses to health-related issues. Pre-Exposure Prophylaxis (PrEP) is one of the most effective ways to reduce the risk of HIV infection. However, its utilization is low in the US, especially among populations disproportionately affected by HIV such as the age group of under 24 years old. It is therefore important to understand the barriers to the wider use of PrEP in the US using social media posts. In this study, we collected tweets from Twitter about PrEP in the past 4 years to identify such barriers by first identifying tweets about personal discussions, and then performing textual analysis using word analysis, UMLS semantic type analysis, and topic modeling. We found that the public often discussed advocacy, risks/benefits, access, pricing, insurance coverage, legislation, stigma, health education, and prevention of HIV. This result is consistent with the literature and can help identify strategies for promoting the use of PrEP, especially among young adults.
Neuroinflammation in the amygdala is associated with recent depressive symptoms
Authors: Zhang Wei , Rutlin Jerrel , Eisenstein Sarah A. , Wang Yong , Barch Deanna , Hershey Tamara , Bogdan Ryan , Bijsterbosch Janine 
Published: December 2022

ABSTRACTBackgroundConverging evidence suggests that elevated inflammation may contribute to depression. Yet, the link between peripheral and neuro-inflammation in depression is unclear. Here using data from the UK Biobank (n=11,512), we estimated associations among depression, C-reactive protein as a measure of peripheral inflammation (CRP), and neuroinflammation as indexed by diffusion-basis spectral imaging-based restricted fraction (DBSI-RF).MethodsDBSI-RF was derived from diffusion-weighted imaging data for whole-brain gray matter (global-RF), and regions of interest in bilateral amygdala (amygdala-RF) and hippocampus (hippocampus-RF), and CRP was estimated from blood (serum) samples. Self-reported recent depression symptoms were measured using a 4-item assessment. Linear regressions were used to estimate associations between CRP and DBSI-RFs with depression, while adjusting for the following covariates: Age, sex, body mass index, smoking, drinking, and medical conditions.ResultsElevated CRP was associated with higher depression symptoms (r=0.03, p<0.001) and reduced global-RF (r=-0.03, p<0.005). Higher amygdala-RF was associated with elevated depression – an effect resilient to added covariates and CRP (t=2.53, β=0.02, p<0.05). Interestingly, this association was stronger in individuals with a lifetime history of depression (t=3.02, β=0.07, p<0.005) than in those without (t=2.32, β=0.03, p<0.05). Associations between global-RF or hippocampus-RF with depression were not significant, and no DBSI-RF indices indirectly linked CRP with depression (i.e., mediation effect).ConclusionPeripheral inflammation and DBSI-RF neuroinflammation in the amygdala are independently associated with depression, consistent with animal studies suggesting distinct pathways of peripheral and neuro-inflammation in the pathophysiology of depression, and with investigations highlighting the role of the amygdala in stress-induced inflammation and depression.
ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients
Authors: Song Yufeng , Myers Regan , Murphy Lila , Brooks Bailey , Wilson Jeffrey M. , Kadl Alexandra , Woodfolk Judith , Zeichner Steven L. 
Published: December 2022

AbstractMany mechanisms responsible for COVID-19 pathogenesis are well-established, but COVID-19 includes features with unclear pathogenesis, such as autonomic dysregulation, coagulopathies, and high levels of inflammation. The receptor for SARS-CoV-2 spike protein’s receptor binding domain (RBD) is angiotensin converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop antibodies that have negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity – ACE2-like abzymes. To explore this hypothesis, we studied patients hospitalized with COVID-19 who had plasma samples available obtained about 7 days after admission. ACE2 is a metalloprotease that requires Zn2+for activity. However, we found that the plasma from some patients studied could cleave a synthetic ACE2 peptide substrate, even though the plasma samples were collected using disodium ethylenediaminetetraacetate (EDTA) anticoagulant. When we spiked plasma with synthetic ACE2, no ACE2 substrate cleavage activity was observed unless Zn2+was added or the plasma was diluted to decrease EDTA concentration. After processing samples by 100 kDa size exclusion columns and protein A/G adsorption, which depleted immunoglobulin by >99.99%, the plasma samples did not cleave the ACE2 substrate peptide. The data suggest that some patients with COVID-19 develop antibodies with abzyme-like activity capable of cleaving synthetic ACE2 substrate. Since abzymes can exhibit promiscuous substrate specificities compared to the enzyme whose active site image they resemble, and since proteolytic cascades regulate many physiologic processes, anti-RBD abzymes may contribute to some otherwise obscure COVID-19 pathogenesis.
Changing social contact patterns among US workers during the COVID-19 pandemic: April 2020 to December 2021
Authors: Kiti Moses C. , Aguolu Obianuju G. , Zelaya Alana , Chen Holin Y. , Ahmed Noureen , Battross Jonathan , Liu Carol Y. , Nelson Kristin N. , Jenness Samuel M. , Melegaro Alessia , Ahmed Faruque , Malik Fauzia , Omer Saad B. , Lopman Ben A. 
Published: December 2022

AbstractNon-pharmaceutical interventions minimize social contacts, hence the spread of SARS-CoV-2. We quantified two-day contact patterns among USA employees from 2020–2021 during the COVID-19 pandemic. Contacts were defined as face-to-face conversations, involving physical touch or proximity to another individual and were collected using electronic diaries. Mean (standard deviation) contacts reported by 1,456 participants were 2.5 (2.5), 8.2 (7.1), 9.2 (7.1) and 10.1 (9.5) across round 1 (April–June 2020), 2 (November 2020–January 2021), 3 (June–August 2021), and 4 (November–December 2021), respectively. Between round 1 and 2, we report a 3-fold increase in the mean number of contacts reported per participant with no major increases from round 2–4. We modeled SARS-CoV-2 transmission at home, work, and community. The model revealed reduced relative transmission in all settings in round 1. Subsequently, transmission increased at home and in the community but remained very low in work settings. Contact data are important to parameterize models of infection transmission and control.TeaserChanges in social contact patterns shape disease dynamics at workplaces in the USA.
Utilizing co-abundances of antimicrobial resistance genes to identify potential co-selection in the resistome
Authors: Martiny Hannah-Marie , Munk Patrick , Brinch Christian , Aarestrup Frank M. , Calle M. Luz , Petersen Thomas N. 
Published: December 2022

AbstractThe rapid spread of antimicrobial resistance (AMR) is a threat to global health, and the nature of co-occurring antimicrobial resistance genes (ARGs) may cause collateral AMR effects once antimicrobial agents are used. Therefore, it is essential to identify which pairs of ARGs co-occur. Given the wealth of NGS data available in public repositories, we have investigated the correlation between ARG abundances in a collection of 214,095 metagenomic datasets. Using more than 6.76·108read fragments aligned to acquired ARGs to infer pairwise correlation coefficients, we found that more ARGs correlated with each other in human and animal sampling origins than in soil and water environments. Furthermore, we argued that the correlations could serve as risk profiles of resistance co-occurring to critically important antimicrobials. Using these profiles, we found evidence of several ARGs conferring resistance for critically important antimicrobials (CIA) being co-abundant, such as tetracycline ARGs correlating with most other forms of resistance. In conclusion, this study highlights the important ARG players indirectly involved in shaping the resistomes of various environments that can serve as monitoring targets in AMR surveillance programs.