bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fungal sporocarps house diverse and host-specific communities of fungicolous fungi
Authors: Maurice Sundy , Arnault Gontran , Nordén Jenni , Botnen Synnøve Smebye , Miettinen Otto , Kauserud Håvard 
Published: January 2021

AbstractSporocarps (fruit bodies) are the sexual reproductive stage in the life cycle of many fungi. They are highly nutritious and consequently vulnerable to grazing by birds and small mammals, and invertebrates, and can be infected by microbial and fungal parasites and pathogens. The complexity of communities thriving inside sporocarps is largely unknown. In this study, we revealed the diversity, taxonomic composition and host preference of fungicolous fungi (i.e., fungi that feed on other fungi) in sporocarps. We carried out DNA metabarcoding of the ITS2 region from 176 sporocarps of 11 wood-decay fungal host species, all collected within a forest in northeast Finland. We assessed the influence of sporocarp traits, such as lifespan, morphology and size, on the fungicolous fungal community. The level of colonisation by fungicolous fungi, measured as the proportion of non-host ITS2 reads, varied between 2.8–39.8% across the 11 host species and was largely dominated by Ascomycota. Host species was the major determinant of the community composition and diversity of fungicolous fungi, suggesting that host adaptation is important for many fungicolous fungi. Furthermore, the alpha diversity was consistently higher in short-lived and resupinate sporocarps compared to long-lived and pileate ones, perhaps due to a more hostile environment for fungal growth in the latter too. The fungicolous fungi represented numerous lineages in the fungal tree of life, among which a significant portion was poorly represented with reference sequences in databases.
Hard for humans, hard for machines: predicting readmission after psychiatric hospitalization using narrative notes
Authors: Boag William , Kovaleva Olga , McCoy Thomas H. , Rumshisky Anna , Szolovits Peter , Perlis Roy H. 
Published: January 2021

AbstractMachine learning has been suggested as a means of identifying individuals at greatest risk for hospital readmission, including psychiatric readmission. We sought to compare the performance of predictive models that use interpretable representations derived via topic modeling to the performance of human experts and nonexperts. We examined all 5076 admissions to a general psychiatry inpatient unit between 2009 and 2016 using electronic health records. We developed multiple models to predict 180-day readmission for these admissions based on features derived from narrative discharge summaries, augmented by baseline sociodemographic and clinical features. We developed models using a training set comprising 70% of the cohort and evaluated on the remaining 30%. Baseline models using demographic features for prediction achieved an area under the curve (AUC) of 0.675 [95% CI 0.674–0.676] on an independent testing set, while language-based models also incorporating bag-of-words features, discharge summaries topics identified by Latent Dirichlet allocation (LDA), and prior psychiatric admissions achieved AUC of 0.726 [95% CI 0.725–0.727]. To characterize the difficulty of the task, we also compared the performance of these classifiers to both expert and nonexpert human raters, with and without feedback, on a subset of 75 test cases. These models outperformed humans on average, including predictions by experienced psychiatrists. Typical note tokens or topics associated with readmission risk were related to pregnancy/postpartum state, family relationships, and psychosis.
Anomaly detection to predict relapse risk in schizophrenia
Authors: Henson Philip , D’Mello Ryan , Vaidyam Aditya , Keshavan Matcheri , Torous John 
Published: January 2021

AbstractThe integration of technology in clinical care is growing rapidly and has become especially relevant during the global COVID-19 pandemic. Smartphone-based digital phenotyping, or the use of integrated sensors to identify patterns in behavior and symptomatology, has shown potential in detecting subtle moment-to-moment changes. These changes, often referred to as anomalies, represent significant deviations from an individual’s baseline, may be useful in informing the risk of relapse in serious mental illness. Our investigation of smartphone-based anomaly detection resulted in 89% sensitivity and 75% specificity for predicting relapse in schizophrenia. These results demonstrate the potential of longitudinal collection of real-time behavior and symptomatology via smartphones and the clinical utility of individualized analysis. Future studies are necessary to explore how specificity can be improved, just-in-time adaptive interventions utilized, and clinical integration achieved.
Reducing intrusive memories after trauma via a brief cognitive task intervention in the hospital emergency department: an exploratory pilot randomised controlled trial
Authors: Kanstrup Marie , Singh Laura , Göransson Katarina E. , Widoff Julia , Taylor Rod S. , Gamble Beau , Iyadurai Lalitha , Moulds Michelle L. , Holmes Emily A. 
Published: January 2021

AbstractIntrusive memories are common after trauma, and can cause significant distress. Interventions to prevent/reduce the occurrence of this core clinical feature of posttraumatic stress disorder are needed; they should be easy to deliver, readily disseminated and scalable. A novel one-session intervention by Iyadurai et al. 2018, Molecular Psychiatry, resulted in intrusion reduction over the subsequent week. Its feasibility in a different setting and longer-term effects (>1 month) need investigation. We conducted an exploratory open-label pilot randomised controlled trial (RCT) to investigate the feasibility and effects of a brief behavioural intervention to reduce intrusive memories in trauma-exposed patients in a Swedish hospital emergency department (ED). Participants (final N = 41) were randomly allocated to either intervention (including memory reminder cue then visuospatial cognitive task “Tetris” with mental rotation instructions) or active control (podcast) condition within 72 h of presenting to the ED (both conditions using their smartphone). Findings were examined descriptively. We estimated between-group effect sizes for the number of intrusive memories post-intervention at week 1 (primary outcome) and week 5 (secondary outcome). Compared to the control condition, participants in the intervention condition reported fewer intrusive memories of trauma, both at week 1 and week 5. Findings extend the previous evaluation in the UK. The intervention was readily implemented in a different international context, with a mixed trauma sample, with treatment gains maintained at 1 month and associated with some functional improvements. Findings inform future trials to evaluate the capacity of the cognitive task intervention to reduce the occurrence of intrusive memories after traumatic events.
Gray and white matter morphology in substance use disorders: a neuroimaging systematic review and meta-analysis
Authors: Pando-Naude Victor , Toxto Sebastian , Fernandez-Lozano Sofia , Parsons Christine E. , Alcauter Sarael , Garza-Villarreal Eduardo A. 
Published: January 2021

AbstractSubstance use disorders (SUDs) are characterized by a compulsion to seek and consume one or more substances of abuse, with a perceived loss of control and a negative emotional state. Prolonged substance use seems to be associated with morphological changes of multiple neural circuits, in particular the frontal–striatal and limbic pathways. Such neuroadaptations are evident across several substance disorders, but may vary depending on the type of substance, consumption severity and/or other unknown factors. We therefore identified studies investigating the effects of SUDs using volumetric whole-brain voxel-based morphometry (VBM) in gray (GM) and white matter (WM). We performed a systematic review and meta-analysis of VBM studies using the anatomic likelihood estimation (ALE) method implemented in GingerALE (PROSPERO pre-registrationCRD42017071222). Sixty studies met inclusion criteria and were included in the final quantitative meta-analysis, with a total of 614 foci, 94 experiments and 4938 participants. We found convergence and divergence in brain regions and volume effects (higher vs. lower volume) in GM and WM depending on the severity of the consumption pattern and type of substance used. Convergent pathology was evident across substances in GM of the insula, anterior cingulate cortex, putamen, and thalamus, and in WM of the thalamic radiation and internal capsule bundle. Divergent pathology between occasional use (cortical pathology) and addiction (cortical-subcortical pathology) provides evidence of a possible top-down neuroadaptation. Our findings indicate particular brain morphometry alterations in SUDs, which may inform our understanding of disease progression and ultimately therapeutic approaches.
Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families
Authors: Guzman-Parra Jose , Streit Fabian , Forstner Andreas J. , Strohmaier Jana , González Maria José , Gil Flores Susana , Cabaleiro Fabeiro Francisco J. , del Río Noriega Francisco , Perez Perez Fermin , Haro González Jesus , Orozco Diaz Guillermo , de Diego-Otero Yolanda , Moreno-Kustner Berta , Auburger Georg , Degenhardt Franziska , Heilmann-Heimbach Stefanie , Herms Stefan , Hoffmann Per , Frank Josef , Foo Jerome C. , Sirignano Lea , Witt Stephanie H. , Cichon Sven , Rivas Fabio , Mayoral Fermín , Nöthen Markus M. , Andlauer Till F. M. , Rietschel Marcella 
Published: January 2021

AbstractThe two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development.
A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation of striatal dopamine binding in autism
Authors: Zürcher Nicole R. , Walsh Erin C. , Phillips Rachel D. , Cernasov Paul M. , Tseng Chieh-En J. , Dharanikota Ayarah , Smith Eric , Li Zibo , Kinard Jessica L. , Bizzell Joshua C. , Greene Rachel K. , Dillon Daniel , Pizzagalli Diego A. , Izquierdo-Garcia David , Truong Kinh , Lalush David , Hooker Jacob M. , Dichter Gabriel S. 
Published: January 2021

AbstractThe social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPNDdifferences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.
Development and external validation of an admission risk prediction model after treatment from early intervention in psychosis services
Authors: Puntis Stephen , Whiting Daniel , Pappa Sofia , Lennox Belinda 
Published: January 2021

AbstractEarly Intervention in psychosis (EIP) teams are the gold standard treatment for first-episode psychosis (FEP). EIP is time-limited and clinicians are required to make difficult aftercare decisions that require weighing up individuals’ wishes for treatment, risk of relapse, and health service capacity. Reliable decision-making tools could assist with appropriate resource allocation and better care. We aimed to develop and externally validate a readmission risk tool for application at the point of EIP discharge. All persons from EIP caseloads in two NHS Trusts were eligible for the study. We excluded those who moved out of the area or were only seen for assessment. We developed a model to predict the risk of hospital admission within a year of ending EIP treatment in one Trust and externally validated it in another. There were n = 831 participants in the development dataset and n = 1393 in the external validation dataset, with 79 (9.5%) and 162 (11.6%) admissions to inpatient hospital, respectively. Discrimination was AUC = 0.76 (95% CI 0.75; 0.77) in the development dataset and AUC = 0.70 (95% CI 0.66; 0.75) in the external dataset. Calibration plots in external validation suggested an underestimation of risk in the lower predicted probabilities and slight overestimation at predicted probabilities in the 0.1–0.2 range (calibration slope = 0.86, 95% CI 0.68; 1.05). Recalibration improved performance at lower predicted probabilities but underestimated risk at the highest range of predicted probabilities (calibration slope = 1.00, 95% CI 0.79; 1.21). We showed that a tool for predicting admission risk using routine data has good performance and could assist clinical decision-making. Refinement of the model, testing its implementation and further external validation are needed.
ACPA decreases non-small cell lung cancer line growth through Akt/PI3K and JNK pathways in vitro
Authors: Boyacıoğlu Özge , Bilgiç Elif , Varan Cem , Bilensoy Erem , Nemutlu Emirhan , Sevim Duygu , Kocaefe Çetin , Korkusuz Petek 
Published: January 2021

AbstractTherapeutic agents used for non-small cell lung cancer (NSCLC) have limited curative efficacy and may trigger serious adverse effects. Cannabinoid ligands exert antiproliferative effect and induce apoptosis on numerous epithelial cancers. We confirmed that CB1 receptor (CB1R) is expressed in NSCLC cells in this study. Arachidonoylcyclopropylamide (ACPA) as a synthetic, CB1R-specific ligand decreased proliferation rate in NSCLC cells by WST-1 analysis and real-time proliferation assay (RTCA). The half-maximal inhibitory concentration (IC50) dose of ACPA was calculated as 1.39 × 10−12 M. CB1 antagonist AM281 inhibited the antiproliferative effect of ACPA. Flow cytometry and ultrastructural analyzes revealed significant early and late apoptosis with diminished cell viability. Nano-immunoassay and metabolomics data on activation status of CB1R-mediated pro-apoptotic pathways found that ACPA inhibited Akt/PI3K pathway, glycolysis, TCA cycle, amino acid biosynthesis, and urea cycle and activated JNK pathway. ACPA lost its chemical stability after 24 hours tested by liquid chromatography-mass spectrometry (LC–MS/MS) assay. A novel ACPA-PCL nanoparticle system was developed by nanoprecipitation method and characterized. Sustained release of ACPA-PCL nanoparticles also reduced proliferation of NSCLC cells. Our results demonstrated that low dose ACPA and ACPA-PCL nanoparticle system harbor opportunities to be developed as a novel therapy in NSCLC patients that require further in vivo studies beforehand to validate its anticancer effect.
Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site
Authors: Wang Yao , Chen Qian , Jiao Fangzhou , Shi Chunxia , Pei Maohua , Wang Luwen , Gong Zuojiong 
Published: January 2021

AbstractPyroptosis is a new necrosis pattern of hepatocyte during liver inflammation in acute liver failure (ALF). Histone deacetylase 2 (HDAC2) is associated with several pathological conditions in the liver system. The aim of this study is to investigate whether knockdown or pharmacological inhibition of HDAC2 could reduce the level of pyroptosis in ALF through ULK1-NLRP3-pyroptosis pathway. The role of HDAC2 on ULK1-NLRP3-pyroptosis pathway during ALF was detected in clinical samples. The mechanism was investigated in transfected cells or in ALF mouse model. The RNA-sequencing results revealed that ULK1 was a negative target regulatory molecule by HDAC2. During the process of pyroptosis, the HDAC2 exerted the antagonistic effect with ULK1 by the K68 acetylation site in L02 cells. Then the role of HDAC2 on ULK1-NLRP3-pyroptosis pathway in ALF mouse model was also detected. Moreover, the related molecules to ULK1-NLRP3-pyroptosis pathway were verified different expression in normal health donors and clinical ALF patients. HDAC2 in hepatocytes plays a pivotal role in an ULK1-NLRP3 pathway driven auto-amplification of pyroptosis in ALF. One of the important mechanisms is that inhibition HDAC2 to reduce pyroptosis may be by modulating the K68 lysine site of ULK1.
Suppressing BCL-XL increased the high dose androgens therapeutic effect to better induce the Enzalutamide-resistant prostate cancer autophagic cell death
Authors: Xiang Zhendong , Sun Yin , You Bosen , Zhang Meng , Huang Chiping , Yu Junfeng , You Xiangyun , Wu Denglong , Chang Chawnshang 
Published: January 2021

AbstractMost patients with advanced prostate cancer (PCa) initially respond well to androgen deprivation therapy (ADT) with antiandrogens, but most of them eventually become resistant to ADT. Here, we found that the antiandrogen Enzalutamide-resistant (EnzR) PCa cells can be suppressed by hyper-physiological doses of the androgen DHT. Mechanism dissection indicates that while androgens/androgen receptor (AR) can decrease BCL-2 expression to induce cell death, yet they can also simultaneously increase anti-apoptosis BCL-XL protein expression via decreasing its potential E3 ubiquitin ligase, PARK2, through transcriptionally increasing the miR-493-3p expression to target PARK2. Thus, targeting the high dose DHT/AR/miR-493-3p/PARK2/BCL-XL signaling with BCL-XL-shRNA can increase high-dose-DHT effect to better suppress EnzR cell growth via increasing the autophagic cell death. A preclinical study using in vivo mouse model also validated that suppressing BCL-XL led to enhance high dose DHT effect to induce PCa cell death. The success of human clinical trials in the future may help us to develop a novel therapy using high dose androgens to better suppress CRPC progression.
Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome
Authors: Xu Zhihao , Zhou Ying , Liu Muziying , Ma Huan , Sun Liangqi , Zahid Ayesha , Chen Yulei , Zhou Rongbin , Cao Minjie , Wu Dabao , Zhao Weidong , Li Bofeng , Jin Tengchuan 
Published: January 2021

AbstractCytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD–CARD interaction between purified NLRP1CARD and ASCCARD experimentally and the filamentous supramolecular complex formation in an in vitro proteins solution. Moreover, we determined a high-resolution crystal structure of the death domain fold of the human ASCCARD. Mutational and structural analysis revealed three conserved interfaces of the death domain superfamily (Type I, II, and III), which mediate the assembly of the NLRP1CARD/ASCCARD complex. In addition, we validated the role of the three major interfaces of CARDs in assembly and activation of NLRP1 inflammasome in vitro. Our findings suggest a Mosaic model of homotypic CARD interactions for the activation of NLRP1 inflammasome. The Mosaic model provides insights into the mechanisms of inflammasome assembly and signal transduction amplification.
Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies
Authors: Jaune Emilie , Cavazza Elisa , Ronco Cyril , Grytsai Oleksandr , Abbe Patricia , Tekaya Nedra , Zerhouni Marwa , Beranger Guillaume , Kaminski Lisa , Bost Frédéric , Gesson Maeva , Tulic Meri , Hofman Paul , Ballotti Robert , Passeron Thierry , Botton Thomas , Benhida Rachid , Rocchi Stéphane 
Published: January 2021

AbstractIn the search of biguanide-derived molecules against melanoma, we have discovered and developed a series of bioactive products and identified the promising new compound CRO15. This molecule exerted anti-melanoma effects on cells lines and cells isolated from patients including the ones derived from tumors resistant to BRAF inhibitors. Moreover, CRO15 was able to decrease viability of cells lines from a broad range of cancer types. This compound acts by two distinct mechanisms. First by activating the AMPK pathway induced by a mitochondrial disorder. Second by inhibition of MELK kinase activity, which induces cell cycle arrest and activation of DNA damage repair pathways by p53 and REDD1 activation. All of these mechanisms activate autophagic and apoptotic processes resulting in melanoma cell death. The strong efficacy of CRO15 to reduce the growth of melanoma xenograft sensitive or resistant to BRAF inhibitors opens interesting perspective.