bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment practice of vasospasm during endovascular thrombectomy: an international survey
Authors: Jesser J. , Nguyen T. N. , Dmytriw A. A. , Yamagami H. , Miao Z. , Sommer L. J. , Stockero A. , Pfaff J. A. R. , Ospel J. M. , Goyal M. , Patel A. B. , Mendes Pereira V. , Hanning U. , Meyer L. , van Zwam W. , Bendszus M. , Wiesmann M. , Möhlenbruch M. A. , Weyland C. S. 
Published: August 2023

Background and aimThe clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neuro-intervention and therapeutic strategies of iatrogenic vasospasm during EVT.MethodsWe conducted an anonymous international online survey (April 04thto May 15th2023) addressing treatment standards of neurointerventionalists (NI) practicing EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI’s opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis.ResultsIn total, 534 NI from 56 countries responded, of whom 51.5% had performed more than 200 EVT. Vasospasm was considered a complication potentially influencing the patient’s outcome by 52.6% (Group 1) whereas 47.4% did not (Group 2). Physicians in Group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs. 33.9%, p = 0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs. 55.9%; p < 0.001), as well as extracranial vasospasm (61.4% vs. 36.5%, p < 0.001) and intracranial medium-vessel vasospasm (27.1 % vs. 11.2%, p < 0.001), compared to Group 2. In case of a large-vessel vasospasm and residual and amenable medium vessel occlusion during EVT, the study groups showed different treatment strategies. Group 2 continued the EVT immediately more often, without initiating therapy to treat the vasospasm first (9.6% vs 21.1%, p < 0.001).ConclusionThere is disagreement among neurointerventionalists about the clinical relevance of vasospasm during EVT and its management. There was a higher likelihood of use of preventive and active vasodilator treatment in the group that perceived vasospasm as a relevant complication as well as differing interventional strategies for continuing an EVT in the presence of a large-vessel vasospasm.
Frequency-dependent selection of neoantigens fosters tumor immune escape and predicts immunotherapy response
Authors: Chen Shaoqing , Xie Duo , Wang Jiguang , Hu Zheng , Zhou Da 
Published: August 2023

AbstractCancer is an evolutionary process undergoing stringent immune selection. However, recent studies have revealed that certain tumors undergo neutral evolution following the malignant transformation. Here, we propose negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is similar to neutral evolution. With a stochastic model of NFDS, we demonstrated that NFDS promotes early immune evasion in hypermutable tumors, leading to neutral-like evolutionary dynamics with high antigenic heterogeneity and worse response to immune checkpoint blockade (ICB) therapy. Our model also revealed that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, NFDS was validated with whole-exome sequencing datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy. Altogether, our study provides the first quantitative evidence supporting the theory of NFDS in immune-driven cancer evolution. These findings highlight the critical role of NFDS theory in devising more efficient and predictive immunotherapies.
Distinct roles of putative excitatory and inhibitory neurons in the macaque inferior temporal cortex in core object recognition behavior
Authors: Sanghavi Sachi , Kar Kohitij 
Published: August 2023

AbstractA spatially distributed population of neurons in the macaque inferior temporal (IT) cortex supports object recognition behavior, but the cell-type specificity of the population in forming “behaviorally sufficient” object decodes remain unclear. To address this, we recorded neural signals from the macaque IT cortex and compared the object identity information and the alignment of decoding strategies derived from putative inhibitory (Inh) and excitatory (Exc) neurons to the monkeys’ behavior. We observed that while Inh neurons represented significant category information, decoding strategies based on Exc neural population activity outperformed those from Inh neurons in overall accuracy and their image-level match to the monkeys’ behavioral reports. Interestingly, both Exc and Inh responses explained a fraction of unique variance of the monkeys’ behavior, demonstrating a distinct role of the two cell types in generating object identity solutions for a downstream readout. We observed that current artificial neural network (ANN) models of primate ventral stream, designed with AI goals of performance optimization on image categorization, better predict Exc neurons (and its contribution to object recognition behavior) than Inh neurons. Beyond, the refinement of linking propositions between IT and object recognition behavior, our results guide the development of more biologically constrained brain models by offering novel cell-type specific neural benchmarks.
Exome-wide association study reveals 7 functional variants associated with ex-vivo drug response in acute myeloid leukemia patients
Authors: Giri Anil K , Lin Jake , Kyriakidis Konstantinos , Tripathi Garima , Almusa Henrikki 
Published: August 2023

AbstractAcute myeloid leukemia (AML) is a rare aggressive blood cancer without any long-term cure. Further, due to the extreme molecular heterogeneity of the disease, drug treatment response varies from patient to patient. The variability of drug response can cause unnecessary treatment in more than half of the patients with no or partial therapy responses leading to severe side effects, economic as well as time loss. Understanding the genetic risk factors underlying the drug response in AML can help with improved prediction of treatment responses and identification of biomarkers in addition to mechanistic insights to monitor treatment response.Here, we report the results of the largest exome-wide association study (EWAS) of ex-vivo drug response performed to date with 175 AML cases and 47 drugs. We used information from 55423 exonic SNPs to perform the analysis. We identified exome-wide significant (p<9.02 ×10-7) associations for rs113985677 inCCINwith tamoxifen response, rs115400838 inTRMT5with idelalisib response, rs11878277 inHDGFL2with entinostat, and rs2229092 in LTA associated with vorinostat response.Further, using multivariate genome-wide association analysis, we identified the association of rs11556165 inATRAID, and rs11236938 inTSKUwith the combined response of all 47 drugs and 29 nonchemotherapy drugs at the genome-wide significance level (p<5×10-8). Additionally, a significant association of rs35704242 inNIBAN1was associated with the combined response for nonchemotherapy medicines (p=2.51×10-8), and BI.2536, gefitinib, and belinostat were identified as the central traits. Our study represents the largest EWAS study to date on ex-vivo drug response in AML and reports 7 new associated loci that help to understand the anticancer drug response in AML patients.
Impact of γ-herpes viruses’ status on established risk factor profile of oral squamous cell carcinoma tissues in a group of Sri Lankan male
Authors: Perera Manosha Lakmali , Perera Irosha Rukmali 
Published: August 2023

ABSTRACTOral cancer with multifactorial aetiology was established as a public health challenge globally especially locally. Alarmingly, oral cancer ranks 1st among Sri Lankan males and 8thamong Sri Lankan females with 2-3 death daily. Oral squamous cell carcinoma (OSCC) accounts for 90-95% of oral malignancies in most countries. Perhaps, infectious agents are responsible for approximately 20% of global cancer incidence. Among them, Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpes virus (KHSV) are γ-herpes viruses linked with mucosal malignancies also. There is a dearth of information on oncogenic viral infections in oral cancer patients. Thus, the present study aimed to investigate the impact of γ-herpes viruses’ status on the -established risk factor profile of OSCC tissue in a group of Sri Lankan male patients. Ethical approvals were obtained from Sri Lanka and Australia. A large unmatched case-control study was conducted on Oral and Maxillo-Facial Surgical (OMF) units located in six provinces. Consequently, a representative sub-sample of histopathologically confirmed 29 OSCC cases and clinically diagnosed 25 Fibroepithelial-poly (FEP)controls was selected from the main, adhering to stringent inclusion criteria, for cases at least with betel quid chewing, while excluding none of oral risk habits. Incisional biopsies of cases and excisional biopsies of controls were collected, transported, stored, and dispatched as frozen tissues at - 800C. Then, DNA was extracted from frozen specimens. Subsequently, real-time PCR was performed to detect γ-herpes viruses separately. Socio demographic and clinical data were obtained entered and analysed using SPSS-21 Statistical Package. Descriptive statistics and Fisher’s exact test were used to compare groups ((cell counts <5). The overall EBV prevalence was calculated as 34 (64.2%). In OSCC cases the EBV positivity was higher 21(77.8%) than the FEP controls 13 (50.0%), and this difference was statistically significant (p<0.05). Neither cases nor controls infected with KSHV/HHV-8. In oral risk habit comparison, the cases were better substance abusers, especially in terms of betel quid chewing and alcohol consumption than the control group (p<0.05), The impacts of γ-herpes viruses’ status on established risk factors are noteworthy to investigate by adequately powered prospective studies exclusively in local and regional context.
Effect of an intensive lifestyle intervention on the structural and functional substrate for atrial fibrillation in people with metabolic syndrome
Authors: Rossello Xavier , Ramallal Raúl , Romaguera Dora , Alonso-Gómez Ángel M. , Alonso Alvaro , Tojal-Sierra Lucas , Fernández-Palomeque Carlos , Martínez-González Miguel Ángel , Garrido-Uriarte María , López Luis , Díaz Agnes , Zaldua-Irastorza Olatz , Shah Amit J. , Salas-Salvadó Jordi , Fitó Montserrat , Toledo Estefania 
Published: August 2023

ABSTRACTAimsTo evaluate the effect of an intensive lifestyle intervention (ILI) on the structural and functional cardiac substrate of atrial fibrillation (AF) in overweight or obese people with metabolic syndrome (MetS).MethodsParticipants of the PREDIMED-PLUS trial (n=6874) were randomised 1:1 to an ILI program based on an energy-reduced Mediterranean diet, increased physical activity, and cognitive-behavioural weight management, or to a control intervention of low-intensity dietary advice. Left atrial (LA) strain, function, and volumes were evaluated by a core echocardiography lab in 534 participants at baseline, 3-year and 5-year follow-up. Mixed models were used to evaluate the effect of the ILI on LA structure and function.ResultsIn the subsample, baseline mean age was 65 years (SD 5 years), and 40% of the participants were women. Over the 5-year period, both groups experienced worsening of LA structure and function, with increases in LA volumes and stiffness index and decreases in LA longitudinal strain, LA function index and LA emptying fraction over time. Changes in the ILI and control group were not significantly different for any of the primary outcomes (LA emptying fraction: -0.95% (95%CI -0.93, -0.98) in control group, -0.97% (95%CI -0.94, -1.00) in ILI group, pbetween groups=0.80; LA longitudinal strain: 0.82% (95%CI 0.79, 0.85) in control group, 0.85% (95%CI 0.82, 0.89) in ILI group, pbetween groups=0.24) or any of the secondary outcomes.ConclusionsIn overweight or obese people with MetS, an ILI had no impact on the underlying structural and functional left atrial substrate measurements associated with AF risk.
Estimation of the direct health costs attributable to child obesity in Brazil
Authors: Nilson Eduardo Augusto Fernandes , da Costa Michele Gonçalves , Rocha Carolina , Honorio Olivia , Barreto Raphael 
Published: August 2023

AbstractIntroductionChildhood obesity is a major global public health issue globally and in Brazil. The impacts of childhood obesity include higher risk of disease during childhood and of obesity and non-communicable diseases in adulthood and represent an important epidemiological and economic burden to countries.MethodsThis study is based on the modeling of total costs of hospitalizations and the additional costs attributable to childhood obesity in the Brazilian National Health System.ResultsThe hospitalizations of children and adolescents with obesity as a primary cause totaled R$5.5 million to the Brazilian National Health System from 2013 to 2022, demonstrating that obesity is rarely considered as a cause of hospitalization especially among children and adolescents. The additional costs of hospitalizations attributable to childhood obesity totaled R$213.1 million during the same period. Considering the additional non-hospital, outpatient and medication cost attributable to childhood obesity in Brazil, the total costs were estimated at R$225.7 million in the last decade.ConclusionThis study highlight that the costs of childhood obesity are not limited to the impacts on adult health and represent a relevant economic burden to the Brazilian National Health System and to families because of additional costs during childhood. Therefore, the prevention and control of childhood obesity is a public health priority that demands immediate and robust policies.
Post-acute health care costs following SARS-CoV-2 infection: A retrospective cohort study of among 531,182 matched adults
Authors: McNaughton Candace D. , Austin Peter C. , Li Zhiyin , Sivaswamy Atul , Fang Jiming , Abdel-Qadir Husam , Udell Jacob A. , Wodchis Walter , Lee Douglas S. , Mostarac Ivona , Atzema Clare L. 
Published: August 2023

AbstractPost-acute health care costs following SARS-CoV-2 infection are not known. Beginning 56 days following SARS-CoV-2 polymerase chain reaction (PCR) testing, we compared person-specific total and component health care costs across their distribution for the following year (test-positive versus test-negative, matched people; January 1, 2020-March 31, 2021). For 531,182 individuals, mean person-specific total health care costs were $513.83 (95% CI $387.37-$638.40) higher for test-positive females and $459.10 (95% CI $304.60-$615.32) higher for test-positive males, or >10% increase in mean per-capita costs, driven by hospitalization, long-term care, and complex continuing care costs. At the 99thpercentile of each subgroup, person-specific health care costs were $12,533.00 (95% CI $9,008.50-$16,473.00) higher for test-positive females and $14,604.00 (95% CI $9,565.50-$19,506.50) for test-positive males, driven by hospitalization, specialist (males), and homecare costs (females). Cancer costs were lower. Six-month and 1-year costs differences were similar. These findings can inform planning for post-acute SARS-CoV-2 health care costs.
Improving Genetic Association Studies with a Novel Methodology that Unveils the Hidden Complexity of All-Cause Heart Failure
Authors: Gregg John T. , Himes Blanca E. , Asselbergs Folkert W. , Moore Jason H. 
Published: August 2023

AbstractMotivationGenome-Wide Association Studies (GWAS) commonly assume phenotypic and genetic homogeneity that is not present in complex conditions. We designed Transformative Regression Analysis of Combined Effects (TRACE), a GWAS methodology that better accounts for clinical phenotype heterogeneity and identifies gene-by-environment (GxE) interactions. We demonstrated with UK Biobank (UKB) data that TRACE increased the variance explained in All-Cause Heart Failure (AHF) via the discovery of novel single nucleotide polymorphism (SNP) and SNP-by-environment (i.e. GxE) interaction associations. First, we transformed 312 AHF-related ICD10 codes (including AHF) into continuous low-dimensional features (i.e., latent phenotypes) for a more nuanced disease representation. Then, we ran a standard GWAS on our latent phenotypes to discover main effects and identified GxE interactions with target encoding. Genes near associated SNPs subsequently underwent enrichment analysis to explore potential functional mechanisms underlying associations. Latent phenotypes were regressed against their SNP hits and the estimated latent phenotype values were used to measure the amount of AHF variance explained.ResultsOur method identified over 100 main GWAS effects that were consistent with prior studies and hundreds of novel gene-by-smoking interactions, which collectively accounted for approximately 10% of AHF variance. This represents an improvement over traditional GWAS whose results account for a negligible proportion of AHF variance. Enrichment analyses suggested that hundreds of miRNAs mediated the SNP effect on various AHF-related biological pathways. The TRACE framework can be applied to decode the genetics of other complex diseases.AvailabilityAll code is available athttps://github.com/EpistasisLab/latent_phenotype_project
Discovery of a multipotent cell type from the term human placenta
Authors: Vadakke-Madathil Sangeetha , Bouhamida Esmaa , Wang Bingyan J , Mathiyalagan Prabhu , Oniskey Micayla , Santos-Gallegos Carlos , Hadley Michael , Croft Lori , Dekio Fumiko , Brody Rachel , Gelber Shari , Sperling Rhoda , Chaudhry Hina W. 
Published: August 2023

AbstractWe report a population of multipotent cells isolated from term human placentas, for the first time, that differentiates into cardiomyocytes and vascular cells with clonal ability, migratory ability, and trancriptomic evidence of immune privilege. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development but has not previously been implicated in developmentally conserved regenerative mechanisms. We earlier reported that murine Cdx2 cells restored cardiac function after intravenous delivery in male mice with experimental myocardial infarction (MI). Here we demonstrate that CDX2 cells found in human chorion are poised for cardiovascular differentiation. We isolated CDX2 cells from term placentas of 150 healthy patients and showed that they spontaneously differentiate into cardiomyocytes, functional vascular cells, and retain homing abilityin vitrowith a transcriptome that supports enhanced cardiogenesis, vasculogenesis, immune modulation, and chemotaxis gene signatures. They restore cardiac function when administered to NOD/SCID mice subjected to MI. CDX2 cells can be clonally propagated in culture with retention of cardiovascular differentiation. Our data compels further use of this ethically feasible cell source in the design of therapeutic strategies for cardiovascular disease.One-sentence SummaryCDX2 cells from human placenta are poised for cardiovascular differentiation and may lead to a novel therapeutic approach for human heart repair.
Chrombus-XMBD: A Graph Generative Model Predicting 3D-Genome,ab initiofrom Chromatin Features
Authors: Zeng Yuanyuan , You Zhiyu , Guo Jiayang , Zhao Jialin , Zhou Ying , Huang Jialiang , Lyu Xiaowen , Chen Longbiao , Li Qiyuan 
Published: August 2023

AbstractsThe landscape of 3D-genome is crucial for transcription regulation. But capturing the dynamics of chromatin conformation is costly and technically challenging. Here we described “Chrombus-XMBD”, a graph generative model capable of predicting chromatin interactionsab initobased on available chromatin features. Chrombus employes dynamic edge convolution with QKV attention setup, which maps the relevant chromatin features to a learnable embedding space thereby generate genomewide 3D-contactmap. We validated Chrombus predictions with published databases of topological associated domains (TAD), eQTLs and gene-enhancer interactions. Chrombus outperforms existing algorithms in efficiently predicting long-range chromatin interactions. Chrombus also exhibits strong generalizability across different cell lineage and species. Additionally, the parameter sets of Chrombus inform the biological processes underlying 3D-genome. Our model provides a new perspective towards interpretable AI-modeling of the dynamics of chromatin interactions and better understanding ofcis-regulation of gene expression.
Biogenic phosphonate utilization by globally distributed diatomThalassiosira
Authors: Shu Huilin , Shen Yuan , Wang Hongwei , Sun Xueqiong , Ma Jian , Lin Xin 
Published: August 2023

AbstractPhosphonate is a class of enigmatic organic phosphorus compounds that contribute ∼25% of total dissolved organic phosphorus (DOP). Recent studies reveal the important role of phosphonate mediated by prokaryotes in the marine P redox cycle, however, its bioavailability and metabolic process by eukaryotic phytoplankton are under debate. 2-Aminoethylphosphonic acid and (2-AEP) and 2-amino-3-phosphonopropionic acid (2-AP3) are two biogenic phosphonates that ubiquitously exist in marine environment. Here, we report thatThalassiosira pseudonana, a dominant diatom species in the ocean, are able to recover growth from phosphorus starvation with individual supplement of 2-AEP and 2-AP3. Moreover, the cellular stoichiometric C:P and N:P ratios of cells grown under 2-AEP are in-between the P-depleted and DIP-replete groups. This study provided evidence that biogenic phosphonates can be adopted as alternative phosphorus sources to support diatom growth and might have a profound effect on the elemental stoichiometry in the oligotrophic ocean.Scientific significance statementPhosphorus (P) is a major limiting macronutrient for primary productivity in the ocean, whilst the biologically mediated cycling of different P forms is less understood compared to carbon and nitrogen. Accounting for 25% of the marine dissolved organic phosphorus pool, phosphonate bioavailability by eukaryotic phytoplankton still remains discrepancies. In line with our hypothesis, here we report that a cosmopolitan diatomThalassiosira pseudonanacan utilize biogenic phosphonates 2-aminoethylphosphonic acid and 2-amino-3-phosphonopropionic acid to support cell growth, with deviated cellular C:N:P in comparison to that of P-replete cells. Furthermore, cells grown under lower temperature exhibit physiological adaptation (K-selection strategy) with the benefit of 2-AEP supplied in the medium. We provide the evidence that utilization of biogenic phosphonate is ubiquitous in diatom and it might have profound effect on elemental stoichiometry ratios in the environment. Filling in this missing puzzle piece provides us with a fresh perspective to elucidate the role of phosphonates in marine phosphorus cycle and biological pump.