bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new ferroptosis-related genetic mutation risk model predicts the prognosis of skin cutaneous melanoma
Authors: He Jia , Huang Wenting , Li Xinxin , Wang Jingru , Nie Yaxing , Li Guiqiang , Wang Xiaoxiang , Cao Huili , Chen Xiaodong , Wang Xusheng 
Published: January 2023

Background: Ferroptosis is an iron-dependent cell death mode and closely linked to various cancers, including skin cutaneous melanoma (SKCM). Although attempts have been made to construct ferroptosis-related gene (FRG) signatures for predicting the prognosis of SKCM, the prognostic impact of ferroptosis-related genetic mutations in SKCM remains lacking. This study aims to develop a prediction model to explain the relationship between ferroptosis-related genetic mutations and clinical outcomes of SKCM patients and to explore the potential value of ferroptosis in SKCM treatment.Methods: FRGs which significantly correlated with the prognosis of SKCM were firstly screened based on their single-nucleotide variant (SNV) status by univariate Cox regression analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) and Cox regressions were performed to construct a new ferroptosis-related genetic mutation risk (FerrGR) model for predicting the prognosis of SKCM. We then illustrate the survival and receiver operating characteristic (ROC) curves to evaluate the predictive power of the FerrGR model. Moreover, independent prognostic factors, genomic and clinical characteristics, immunotherapy, immune infiltration, and sensitive drugs were compared between high—and low—FerrGR groups.Results: The FerrGR model was developed with a good performance on survival and ROC analysis. It was a robust independent prognostic indicator and followed a nomogram constructed to predict prognostic outcomes for SKCM patients. Besides, FerrGR combined with tumor mutational burden (TMB) or MSI (microsatellite instability) was considered as a combined biomarker for immunotherapy response. The high FerrGR group patients were associated with an inhibitory immune microenvironment. Furthermore, potential drugs target to high FerrGR samples were predicted.Conclusion: The FerrGR model is valuable to predict prognosis and immunotherapy in SKCM patients. It offers a novel therapeutic option for SKCM.
IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study
Authors: Shojaei Maryam , Shamshirian Amir , Monkman James , Grice Laura , Tran Minh , Tan Chin Wee , Teo Siok Min , Rodrigues Rossi Gustavo , McCulloch Timothy R. , Nalos Marek , Raei Maedeh , Razavi Alireza , Ghasemian Roya , Gheibi Mobina , Roozbeh Fatemeh , Sly Peter D. , Spann Kirsten M. , Chew Keng Yih , Zhu Yanshan , Xia Yao , Wells Timothy J. , Senegaglia Alexandra Cristina , Kuniyoshi Carmen Lúcia , Franck Claudio Luciano , dos Santos Anna Flavia Ribeiro , Noronha Lucia de , Motamen Sepideh , Valadan Reza , Amjadi Omolbanin , Gogna Rajan , Madan Esha , Alizadeh-Navaei Reza , Lamperti Liliana , Zuñiga Felipe , Nova-Lamperti Estefania , Labarca Gonzalo , Knippenberg Ben , Herwanto Velma , Wang Ya , Phu Amy , Chew Tracy , Kwan Timothy , Kim Karan , Teoh Sally , Pelaia Tiana M. , Kuan Win Sen , Jee Yvette , Iredell Jon , O’Byrne Ken , Fraser John F. , Davis Melissa J. , Belz Gabrielle T. , Warkiani Majid E. , Gallo Carlos Salomon , Souza-Fonseca-Guimaraes Fernando , Nguyen Quan , Mclean Anthony , Kulasinghe Arutha , Short Kirsty R. , Tang Benjamin 
Published: January 2023

PurposeRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.ResultsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.ConclusionThese data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.
SARS-CoV-2 antibody response after mRNA vaccination in healthcare workers with and without previous COVID-19, a follow-up study from the University Hospital in Krakow, Poland
Authors: Owsianka Izabella , Pac Agnieszka , Jachowicz Estera , Gutkowska Karolina , Szczuciński Wiktor , Maziarz Barbara , Sochacka-Tatara Elżbieta , Heczko Piotr , Sydor Wojciech , Żółtowska Barbara , Wójkowska-Mach Jadwiga 
Published: January 2023

IntroductionHealthcare workers (HCWs) from the beginning of the pandemic have been at risk of exposure to SARS-CoV-2, so they were vaccinated as first.ObjectivesThe purpose of the study was to determine the level of antibodies against SARS-CoV-2 in HCWs before and after vaccination with mRNA preparations according to previous COVID- 19.Patients and methodsThe HCWs from the University Hospital in Krakow completed two surveys: the baseline survey before receiving the first dose of vaccine (in January 2021) and the follow-up survey in June 2021. In parallel, two blood samples were collected from each participant at baseline and at follow-up. Total anti-SARS-CoV-2 antibody levels were measured using the ECLIA technique.ResultsAt baseline, 41.1% of HCWs had positive antibody test results, and at follow-up, the vaccinated HCWs had almost 100 times higher antibody levels than the unvaccinated HCWs. Participants under 30 years of age had significantly higher antibody levels in June than older HCWs. Among participants with positive antibody test results in January, HCWs who had experienced asymptomatic COVID-19 had more than five times higher antibody levels in June than HCWs self-reported severe COVID-19. In total, 86.9% of HCWs received Comirnaty or Spikevax. The incidence rate of COVID-19 in the unvaccinated vs. vaccinated group was 13 times higher, 20.5% and 1.9% respectively.ConclusionsThese results confirm the effectiveness of vaccination in the prevention of COVID-19 in HCWs. It is worth getting vaccinated regardless of previous infection. Furthermore, vaccination among HCWs under 30 years of age induced more effective antibody production compared to older individuals.
A CRISPR/Cas9-mediated screen identifies determinants of early plasma cell differentiation
Authors: Xiong Ermeng , Popp Oliver , Salomon Claudia , Mertins Philipp , Kocks Christine , Rajewsky Klaus , Chu Van Trung 
Published: January 2023

IntroductionThe differentiation of B cells into antibody-secreting plasma cells depends on cell division-coupled, epigenetic and other cellular processes that are incompletely understood.MethodsWe have developed a CRISPR/Cas9-based screen that models an early stage of T cell-dependent plasma cell differentiation and measures B cell survival or proliferation versus the formation of CD138+ plasmablasts. Here, we refined and extended this screen to more than 500 candidate genes that are highly expressed in plasma cells.ResultsAmong known genes whose deletion preferentially or mostly affected plasmablast formation were the transcription factors Prdm1 (BLIMP1), Irf4 and Pou2af1 (OBF-1), and the Ern1 gene encoding IRE1a, while deletion of XBP1, the transcriptional master regulator that specifies the expansion of the secretory program in plasma cells, had no effect. Defective plasmablast formation caused by Ern1 deletion could not be rescued by the active, spliced form of XBP1 whose processing is dependent on and downstream of IRE1a, suggesting that in early plasma cell differentiation IRE1a acts independently of XBP1. Moreover, we newly identified several genes involved in NF-kB signaling (Nfkbia), vesicle trafficking (Arf4, Preb) and epigenetic regulators that form part of the NuRD complex (Hdac1, Mta2, Mbd2) to be required for plasmablast formation. Deletion of ARF4, a small GTPase required for COPI vesicle formation, impaired plasmablast formation and blocked antibody secretion. After Hdac1 deletion plasmablast differentiation was consistently reduced by about 50%, while deletion of the closely related Hdac2 gene had no effect. Hdac1 knock-out led to strongly perturbed protein expression of antagonistic transcription factors that govern plasma cell versus B cell identity (by decreasing IRF4 and BLIMP1 and increasing BACH2 and PAX5).DiscussionTaken together, our results highlight specific and non-redundant roles for Ern1, Arf4 and Hdac1 in the early steps of plasma cell differentiation.
Comprehensive comparative analysis of prognostic value of serum systemic inflammation biomarkers for colorectal cancer: Results from a large multicenter collaboration
Authors: Xie Hailun , Ruan Guotian , Wei Lishuang , Zhang Heyang , Ge Yizhong , Zhang Qi , Song Mengmeng , Zhang Xi , Liu Xiaoyue , Lin Shiqi , Yang Ming , Hu Chunlei , Tang Meng , Deng Li , Hu Wen , Shi Hanping 
Published: January 2023

BackgroundThe incidence of colorectal cancer (CRC) is common and reliable biomarkers are lacking. We aimed to systematically and comprehensively compare the ability of various combinations of serum inflammatory signatures to predict the prognosis of CRC. Moreover, particular attention has been paid to the clinical feasibility of the newly developed inflammatory burden index (IBI) as a prognostic biomarker for CRC.MethodsThe discrimination capacity of the biomarkers was compared using receiver operating characteristic curves and Harrell’s C-index. Kaplan-Meier curves and log-rank tests were used to compare survival differences between the groups. Cox proportional hazard regression analysis was used to determine the independent prognostic factors. Logistic regression analysis was used to assess the relationship between IBI, short-term outcomes, and malnutrition.ResultsIBI had the optimal prediction accuracy among the systemic inflammation biomarkers for predicting the prognosis of CRC. Taking IBI as a reference, none of the remaining systemic inflammation biomarkers showed a gain. Patients with high IBI had significantly worse overall survival than those with low IBI (56.7% vs. 80.2%; log-rank P&lt;0.001). Multivariate Cox regression analysis showed that continuous IBI was an independent risk factor for the prognosis of CRC patients (hazard ratio = 1.165, 95% confidence interval [CI] = 1.043–1.302, P&lt;0.001). High IBI was an independent risk factor for short-term outcomes (odds ratio [OR] = 1.537, 95% CI = 1.258–1.878, P&lt;0.001), malnutrition (OR = 2.996, 95% CI = 1.471–6.103, P=0.003), and recurrence (OR = 1.744, 95% CI = 1.176–2.587, p = 0.006) in CRC patients.ConclusionsIBI, as a reflection of systemic inflammation, is a feasible and promising biomarker for assessing the prognosis of CRC patients.
Clinical outcomes and characteristics of critically ill patients with influenza- and COVID-19-induced ARDS: A retrospective, matched cohort study
Authors: Volkov Lev , Delpuech Marion , Conrad Marie , Courte Guilhem , Cravoisy Aurélie , Nace Lionel , Baumann Cedric , Gibot Sébastien 
Published: January 2023

IntroductionSeasonal epidemic influenza and SARS-CoV-2 are the most frequent viruses causing acute respiratory distress syndrome (ARDS). To what extent these two etiologies differ in ICU patients remains uncertain. We, therefore, aimed at comparing the severity and outcomes of influenza and SARS-CoV-2-induced ARDS in mechanically ventilated patients.MethodsThis retrospective, analytic, single-center study was conducted in the medical ICU of Nancy University Hospital in France. Adult patients hospitalized with confirmed influenza (from 2009 to 2019) or SARS-CoV-2-induced ARDS (between March 2020 and May 2021) and those under mechanical ventilation were included. Each patient with influenza was matched with two patients with COVID-19, with the same severity of ARDS. The primary endpoint was death in ICU on day 28. The secondary endpoints were the duration of vasopressors, the use of renal replacement therapy, the duration of mechanical ventilation, and the ICU length of stay.ResultsA total of 42 patients with influenza were matched with 84 patients with COVID-19. They had similar sex distribution, age, Charlson comorbidity index, and ARDS severity. On day 28, 11 (26.2%) patients in the influenza group and nine (10.7%) patients in the COVID-19 group had died (p = 0.0084, HR = 3.31, CI 95% [1.36–8.06]). In the univariate Cox model, being infected with SARS-CoV-2, SOFA and SAPS II scores, initial arterial pH, PaCO2, PaO2/FiO2, serum lactate level, platelet count, and use of renal replacement therapy were significantly associated with mortality. In the multivariate Cox model, the SOFA score at admission (p &lt; 0.01, HR = 1.284, CI 95% [1.081; 1.525]) and the initial pH (p &lt; 0.01, HR = 0.618, CI 95% [0.461; 0.828]) were the only predictors of mortality. The type of virus had no influence on mortality, though patients with COVID-19 underwent longer mechanical ventilation and received more neuromuscular blockers and prone positioning.ConclusionIn mechanically ventilated patients with ARDS, 28-day mortality was higher among patients with influenza as compared to patients with COVID-19 because of a higher initial extra-pulmonary severity. However, the type of virus was not, by itself, correlated with mortality.
Phytotoxic Azaphilones From the Mangrove-Derived Fungus Penicillium sclerotiorum HY5
Authors: Wang Wei , Wang Mei , Wang Xian-Bo , Li Yi-Qiang , Ding Ji-Lin , Lan Ming-Xian , Gao Xi , Zhao Dong-Lin , Zhang Cheng-Sheng , Wu Guo-Xing 
Published: January 2023

Graphical AbstractRepresentative phytotoxic azaphilones from Penicillium sclerotiorum HY5.
Morphologic brain network predicts levodopa responsiveness in Parkinson disease
Authors: Xie Yongsheng , Gao Chunyan , Wu Bin , Peng Liling , Wu Jianjun , Lang Liqin 
Published: January 2023

BackgroundThe levodopa challenge test (LCT) has been routinely used in Parkinson disease (PD) evaluation and predicts the outcome of deep brain stimulation (DBS). Guidelines recommend that patients with an improvement in Unified Parkinson’s Disease Rating Scale (UPDRS)-III score &gt; 33% in the LCT receive DBS treatment. However, LCT results are affected by many factors, and only provide information on the immediate effectiveness of dopamine. The aim of the present study was to investigate the relationship between LCT outcome and brain imaging features of PD patients to determine whether the latter can be used to identify candidates for DBS.MethodsA total of 38 PD patients were enrolled in the study. Based on improvement in UPDRS-III score in the LCT, patients were divided into low improvement (PD-LCT-L) and high improvement (PD-LCT-H) groups. Each patient’s neural network was reconstructed based on T1-weighted magnetic resonance imaging data using the Jensen–Shannon divergence similarity estimation method. The network was established with the multiple kernel support vector machine technique. We analyzed differences in individual morphologic brain networks and their global and local metrics to determine whether there were differences in the connectomes of PD-LCT-L and PD-LCT-H groups.ResultsThe 2 groups were similar in terms of demographic and clinical characteristics. Mean ± SD levodopa responsiveness was 26.52% ± 3.47% in the PD-LCT-L group (N = 13) and 58.66% ± 4.09% in the PD-LCT-H group (N = 25). There were no significant differences between groups in global and local metrics. There were 43 consensus connections that were affected in both groups; in PD-LCT-L patients, most of these connections were decreased whereas those related to the dorsolateral superior frontal gyrus and left cuneus were significantly increased.ConclusionMorphologic brain network assessment is a valuable method for predicting levodopa responsiveness in PD patients, which can facilitate the selection of candidates for DBS.
Parallel learning and cognitive flexibility impairments between Fmr1 knockout mice and individuals with fragile X syndrome
Authors: Schmitt Lauren M. , Arzuaga Anna L. , Dapore Ashley , Duncan Jason , Patel Maya , Larson John R. , Erickson Craig A. , Sweeney John A. , Ragozzino Michael E. 
Published: January 2023

IntroductionFragile X Syndrome (FXS) is a monogenic condition that leads to intellectual disability along with behavioral and learning difficulties. Among behavioral and learning difficulties, cognitive flexibility impairments are among the most commonly reported in FXS, which significantly impacts daily living. Despite the extensive use of the Fmr1 knockout (KO) mouse to understand molecular, synaptic and behavioral alterations related to FXS, there has been limited development of translational paradigms to understand cognitive flexibility that can be employed in both animal models and individuals with FXS to facilitate treatment development.MethodsTo begin addressing this limitation, a parallel set of studies were carried out that investigated probabilistic reversal learning along with other behavioral and cognitive tests in individuals with FXS and Fmr1 KO mice. Fifty-five adolescents and adults with FXS (67% male) and 34 age- and sex-matched typically developing controls (62% male) completed an initial probabilistic learning training task and a probabilistic reversal learning task.ResultsIn males with FXS, both initial probabilistic learning and reversal learning deficits were found. However, in females with FXS, we only observed reversal learning deficits. Reversal learning deficits related to more severe psychiatric features in females with FXS, whereas increased sensitivity to negative feedback (lose:shift errors) unexpectedly appear to be adaptive in males with FXS. Male Fmr1 KO mice exhibited both an initial probabilistic learning and reversal learning deficit compared to that of wildtype (WT) mice. Female Fmr1 KO mice were selectively impaired on probabilistic reversal learning. In a prepotent response inhibition test, both male and female Fmr1 KO mice were impaired in learning to choose a non-preferred spatial location to receive a food reward compared to that of WT mice. Neither male nor female Fmr1 KO mice exhibited a change in anxiety compared to that of WT mice.DiscussionTogether, our findings demonstrate strikingly similar sex-dependent learning disturbances across individuals with FXS and Fmr1 KO mice. This suggests the promise of using analogous paradigms of cognitive flexibility across species that may speed treatment development to improve lives of individuals with FXS.
Neurophysiological and emotional influences on team communication and metacognitive cyber situational awareness during a cyber engineering exercise
Authors: Ask Torvald F. , Knox Benjamin J. , Lugo Ricardo G. , Helgetun Ivar , Sütterlin Stefan 
Published: January 2023

Background: Cyber operations unfold at superhuman speeds where cyber defense decisions are based on human-to-human communication aiming to achieve a shared cyber situational awareness. The recently proposed Orient, Locate, Bridge (OLB) model suggests a three-phase metacognitive approach for successful communication of cyber situational awareness for good cyber defense decision-making. Successful OLB execution implies applying cognitive control to coordinate self-referential and externally directed cognitive processes. In the brain, this is dependent on the frontoparietal control network and its connectivity to the default mode network. Emotional reactions may increase default mode network activity and reduce attention allocation to analytical processes resulting in sub-optimal decision-making. Vagal tone is an indicator of activity in the dorsolateral prefrontal node of the frontoparietal control network and is associated with functional connectivity between the frontoparietal control network and the default mode network.Aim: The aim of the present study was to assess whether indicators of neural activity relevant to the processes outlined by the OLB model were related to outcomes hypothesized by the model.Methods: Cyber cadets (N = 36) enrolled in a 3-day cyber engineering exercise organized by the Norwegian Defense Cyber Academy participated in the study. Differences in prospective metacognitive judgments of cyber situational awareness, communication demands, and mood were compared between cyber cadets with high and low vagal tone. Vagal tone was measured at rest prior to the exercise. Affective states, communication demands, cyber situational awareness, and metacognitive accuracy were measured on each day of the exercise.Results: We found that cyber cadets with higher vagal tone had better metacognitive judgments of cyber situational awareness, imposed fewer communication demands on their teams, and had more neutral moods compared to cyber cadets with lower vagal tone.Conclusion: These findings provide neuroergonomic support for the OLB model and suggest that it may be useful in education and training. Future studies should assess the effect of OLB-ing as an intervention on communication and performance.