Miracle-dz/UniFAR-FTUs huggingface dataset:
Ocean warming threatens key trophic interactions supporting a commercial fishery in a climate change hotspot

Worldwide, rising ocean temperatures are causing declines and range shifts in marine species. The direct effects of climate change on the biology of marine organisms are often well documented; yet, knowledge on the indirect effects, particularly through trophic interactions, is largely lacking. We provide evidence of ocean warming decoupling critical trophic interactions supporting a commercially important mollusc in a climate change hotspot. Dietary assessments of the Australian blacklip abalone (Haliotis rubra) indicate primary dependency on a widespread macroalgal species (Phyllospora comosa) which we show to be in state of decline due to ocean warming, resulting in abalone biomass reductions. Niche models suggest further declines in P. comosa over the coming decades and ongoing risks to H. rubra. This study highlights the importance of studies from climate change hotspots and understanding the interplay between climate and trophic interactions when determining the likely response of marine species to environmental changes.
hsa_circ_0000006 induces tumorigenesis through miR-361-3p targeting immunoglobulin-like domains protein 1 (LRIG1) in osteosarcoma

Background Osteosarcoma (OS) is considered to be the most highly prevalent bone tumor. In the progression of different human cancers, the role of circular RNAs (circRNAs) has been extensively studied. Microarray analysis has indicated that hsa_circ_0000006 expression was lower in OS, but the mechanism of hsa_circ_0000006 in regulating the progression of OS remains elusive. Methods The expression of cancer-related genes at the transcriptional and translational levels was assessed by RT-qPCR and western blotting (WB). Colony formation and Cell Counting Kit-8 (CCK-8) assays were used to evaluate the proliferative potential of cells. The transwell assay was used to examine the invasive and migratory potential of cells. Furthermore, dual-luciferase reporter (DLR) and RNA pull-down assays were performed for the validation of the targeting sites of hsa_circ_0000006, miR-361-3p, and the 3'-untranslated region (3'-UTR) of immunoglobulin-like domains protein 1 (LRIG1) mRNA. Moreover, the protein levels of epithelial-to-mesenchymal transition (EMT) markers were analyzed by WB. Results The expression of hsa_circ_0000006 and LRIG1 were found to be down-regulated in OS tissues and cells, while miR-361-3p was up-regulated. Knockdown of hsa_circ_0000006 promoted the progression and development of OS, as well as EMT. Furthermore, hsa_circ_0000006 was revealed as a sponge of miR-361-3p, which negatively regulates miR-361-3p expression. LRIG1 was found to be an miR-361-3p target. In OS cells, the LRIG1 expression level was decreased, with elevated expression of miR-361-3p. Advanced studies demonstrated that hsa_circ_0000006 regulates LRIG1 expression through sponging miR-361-3p, then promotes the tumorigenesis of OS. Conclusions hsa_circ_0000006 is associated with the progression and development of OS through miR-361-3p by target LRIG1, which is a significant biomarker and effective therapeutic target for patients with OS.
Identification of autophagy-related long non-coding RNA prognostic and immune signature for clear cell renal cell carcinoma

Background Studies over the past decade have shown that long non-coding RNAs (lncRNAs) play an essential role in the tumorigenesis and progression of kidney renal clear cell carcinoma (KIRC). Meanwhile, autophagy has been demonstrated to regulate KIRC pathogenesis and targeting therapy resistance. However, the prognostic value of autophagy-related lncRNAs in KIRC patients has not been reported before. Methods In this study, we obtained transcriptome data of 611 KIRC cases from the TCGA database and 258 autophagy-related mRNAs from the HADb database to identify autophagy-related lncRNAs by co-expression network. A prognostic model was then established basing on these autophagy-related lncRNAs, dividing patients into high-risk and low-risk groups. Survival analysis, clinical variables dependent receiver operating characteristic (ROC) analyses, univariate/multivariate Cox analyses, and clinical correlation analysis were performed based on risk signature with R language. Gene set enrichment analysis (GSEA) was then performed to investigate the potential mechanism of the risk signature promoting KIRC progression with GSEA software. CIBERSORT algorithm was performed to assess the impact of these lncRNAs on the infiltration of immune cells. Results A total of 17 lncRNAs were screened out and all these lncRNAs were found significantly related to KIRC patients’ overall survival in subsequent survival analyses. Besides, the overall survival time in the high-risk group was much poorer than in the low-risk group. The ROC analysis revealed that the prognostic value of risk signature was better than age, gender, grade, and N stage. Univariate/multivariate analyses suggested that the risk signature was an independent predictive factor for KIRC patients. Immune and autophagy related pathways were dramatically enriched in high-risk and low-risk groups, respectively, and lncRNAs related immune cells were identified by CIBERSORT. Conclusions In summary, our identified 17 autophagy-related lncRNAs had prognostic value for KIRC patients which may function in immunomodulation.
Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF

Hausmann et al. describe a sentinel intercrypt macrophage population in the intestine, which detects Gram-negative microbes breaching the epithelial barrier and elicits epithelial NF-κB signaling in neighboring crypts. The tunability of this crypt-scale response allows the induction of appropriately scaled defenses according to the localization and intensity of microbial triggers.
Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas

Background N6-methyladenosine (m6A) RNA methylation regulators play crucial role in tumorigenicity and progression. However, their biological significance in primary glioblastomas (GBM) has not been fully elucidated. Methods In the present study, we evaluated the 22 m6A RNA regulators using the integrated data of primary GBM samples from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The different m6A modification patterns and m6A-related gene signature in primary GBM were distinguished by using principal component analysis. Single-sample gene set enrichment analysis was introduced to assess the relative level of immune infiltration. Gene set variation analysis was performed to calculate the enrichment score of the signaling pathways for different clusters. An m6A scoring scheme was established to evaluate the m6A modification pattern in individual tumors in order to predict prognosis and evaluate tumor microenvironment (TME) cell infiltration, immune response, and chemotherapy effect in primary GBM. Results Two distinct m6A modification subgroups associated with different clinical features and biological pathways were identified among the 371 primary GBM. Based on 132 prognostic m6A phenotype-related differentially expressed genes (DEGs) between 2 m6A cluster subgroups, an m6A scoring model was constructed to assess the m6A modification pattern in individual tumors. The high-m6A score group was associated with better prognosis and immune response and worse chemotherapy effect. Conclusions The findings of the present study indicate the potential role of m6A modification in primary GBM, which will help enhance our understanding of TME characteristics, predict clinical prognosis, and provide important insight into effective immunotherapy and chemotherapy.
The Type 2 Diabetes Factor Methylglyoxal Mediates Axon Initial Segment Shortening and Alters Neuronal Function at the Cellular and Network Levels

Abstract Recent evidence suggests that alteration of axon initial segment (AIS) geometry (i.e., length or location along the axon) contributes to CNS dysfunction in neurological diseases. For example, AIS length is shorter in the prefrontal cortex of type 2 diabetic mice with cognitive impairment. To determine the key type 2 diabetes-related factor that produces AIS shortening we modified levels of insulin, glucose, or the reactive glucose metabolite methylglyoxal in cultures of dissociated cortices from male and female mice and quantified AIS geometry using immunofluorescent imaging of the AIS proteins AnkyrinG and βIV spectrin. Neither insulin nor glucose modification altered AIS length. Exposure to 100 but not 1 or 10 μm methylglyoxal for 24 h resulted in accumulation of the methylglyoxal-derived advanced glycation end-product hydroimidazolone and produced reversible AIS shortening without cell death. Methylglyoxal-evoked AIS shortening occurred in both excitatory and putative inhibitory neuron populations and in the presence of tetrodotoxin (TTX). In single-cell recordings resting membrane potential was depolarized at 0.5–3 h and returned to normal at 24 h. In multielectrode array (MEA) recordings methylglyoxal produced an immediate ∼300% increase in spiking and bursting rates that returned to normal within 2 min, followed by a ∼20% reduction of network activity at 0.5–3 h and restoration of activity to baseline levels at 24 h. AIS length was unchanged at 0.5–3 h despite the presence of depolarization and network activity reduction. Nevertheless, these results suggest that methylglyoxal could be a key mediator of AIS shortening and disruptor of neuronal function during type 2 diabetes.
Can ionic concentration changes due to mechanical deformation be responsible for the neurostimulation caused by focused ultrasound? A simulation study

Objective. Ultrasound stimulation is an emerging neuromodulation technique, for which the exact mechanism of action is still unknown. Despite the number of hypotheses such as mechanosensitive ion channels and intermembrane cavitation, they fail to explain all of the observed experimental effects. Here we are investigating the ionic concentration change as a prime mechanism for the neurostimulation by the ultrasound. Approach. We derive the direct analytical relationship between the mechanical deformations in the tissue and the electric boundary conditions for the cable theory equations and solve them for two types of neuronal axon models: Hodgkin–Huxley and C-fibre. We detect the activation thresholds for a variety of ultrasound stimulation cases including continuous and pulsed ultrasound and estimate the mechanical deformations required for reaching the thresholds and generating action potentials (APs). Main results. We note that the proposed mechanism strongly depends on the mechanical properties of the neural tissues, which at the moment cannot be located in literature with the required certainty. We conclude that given certain common linear assumptions, this mechanism alone cannot cause significant effects and be responsible for neurostimulation. However, we also conclude that if the lower estimation of mechanical properties of neural tissues in literature is true, or if the normal cavitation occurs during the ultrasound stimulation, the proposed mechanism can be a prime cause for the generation of APs. Significance. The approach allows prediction and modelling of most observed experimental effects, including the probabilistic ones, without the need for any extra physical effects or additional parameters.
Apixaban and Dalteparin for the Treatment of Venous Thromboembolism in Patients with Different Sites of Cancer

Abstract Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.
Genetic trade-offs underlie divergent life history strategies for local adaptation in white clover.

Local adaptation is common in plants, yet characterization of its underlying genetic basis is rare in herbaceous perennials. Moreover, while many plant species exhibit intraspecific chemical defense polymorphisms, their importance for local adaptation remains poorly understood. We examined the genetic architecture of local adaptation in a perennial, obligately-outcrossing herbaceous legume, white clover (Trifolium repens). This widespread species displays a well-studied chemical defense polymorphism for cyanogenesis (HCN release following tissue damage) and has evolved climate-associated cyanogenesis clines throughout its range. Two biparental F2 mapping populations, derived from three parents collected in environments spanning the U.S. latitudinal species range (Duluth, MN, St. Louis, MO and Gainesville, FL), were grown in triplicate for two years in reciprocal common garden experiments in the parental environments (6,012 total plants). Vegetative growth and reproductive fitness traits displayed trade-offs across reciprocal environments, indicating local adaptation. Genetic mapping of fitness traits revealed a genetic architecture characterized by allelic trade-offs between environments, with 100% and 80% of fitness QTL in the two mapping populations showing significant QTL×E interactions, consistent with antagonistic pleiotropy. Across the genome there were three hotspots of QTL co-localization. Unexpectedly, we found little evidence that the cyanogenesis polymorphism contributes to local adaptation. Instead, divergent life history strategies in reciprocal environments were major fitness determinants: selection favored early investment in flowering at the cost of multi-year survival in the southernmost site vs. delayed flowering and multi-year persistence in the northern environments. Our findings demonstrate that multi-locus genetic tradeoffs contribute to contrasting life history characteristics that allow for local adaptation in this outcrossing herbaceous perennial.
Using Acoustic Speech Patterns From Smartphones to Investigate Mood Disorders: Scoping Review

Background Mood disorders are commonly underrecognized and undertreated, as diagnosis is reliant on self-reporting and clinical assessments that are often not timely. Speech characteristics of those with mood disorders differs from healthy individuals. With the wide use of smartphones, and the emergence of machine learning approaches, smartphones can be used to monitor speech patterns to help the diagnosis and monitoring of mood disorders. Objective The aim of this review is to synthesize research on using speech patterns from smartphones to diagnose and monitor mood disorders. Methods Literature searches of major databases, Medline, PsycInfo, EMBASE, and CINAHL, initially identified 832 relevant articles using the search terms “mood disorders”, “smartphone”, “voice analysis”, and their variants. Only 13 studies met inclusion criteria: use of a smartphone for capturing voice data, focus on diagnosing or monitoring a mood disorder(s), clinical populations recruited prospectively, and in the English language only. Articles were assessed by 2 reviewers, and data extracted included data type, classifiers used, methods of capture, and study results. Studies were analyzed using a narrative synthesis approach. Results Studies showed that voice data alone had reasonable accuracy in predicting mood states and mood fluctuations based on objectively monitored speech patterns. While a fusion of different sensor modalities revealed the highest accuracy (97.4%), nearly 80% of included studies were pilot trials or feasibility studies without control groups and had small sample sizes ranging from 1 to 73 participants. Studies were also carried out over short or varying timeframes and had significant heterogeneity of methods in terms of the types of audio data captured, environmental contexts, classifiers, and measures to control for privacy and ambient noise. Conclusions Approaches that allow smartphone-based monitoring of speech patterns in mood disorders are rapidly growing. The current body of evidence supports the value of speech patterns to monitor, classify, and predict mood states in real time. However, many challenges remain around the robustness, cost-effectiveness, and acceptability of such an approach and further work is required to build on current research and reduce heterogeneity of methodologies as well as clinical evaluation of the benefits and risks of such approaches.
A novel approach to the analysis of spin-trapped free radicals using dimethyl sulfoxide and gas chromatography – mass spectrometry (GC-MS) with both solvent extraction and headspace solid phase microextraction (HS-SPME)

Abstract In this study, we have utilized a novel strategy based upon the use of dimethyl sulfoxide (DMSO) and gas chromatography-mass spectrometry (GC-MS) for the detection and identification of spin-trapped free radicals. Hydroxymethyl ( . CH2OH) radicals, generated by Fenton-type chemistry, have been trapped by N-tert-butyl-α-phenylnitrone (PBN) or one of its derivatives in the presence of DMSO to form a 1,3-diadduct [PBN-(CH2OH)(CH3)], which may be detected directly in the reaction mixture following chloroform extraction or in the reaction vial headspace by sampling with SPME. Separation and identification have been carried out by capillary gas chromatography coupled to electron-ionization mass spectrometry (EI-MS). The results demonstrate that using DMSO aids GC-MS analysis of spin-trapped free radicals via the formation of radical-methyl di-adducts that are sufficiently volatile to be sampled both in the headspace or by an extracting solvent without the need for a derivatization step using silylating agents.
A novel class of ZNF384 aberrations in acute leukemia

Key Points A novel class of ZNF384 aberrations affects the last exon of ZNF384 and results in disruption of the C-terminal portion of ZNF384 protein. Leukemias with the novel class of ZNF384 aberrations phenocopy leukemias with the canonical ZNF384 fusions.
Age and signal strength‐related changes in vessel density in the choroid and the retina: an OCT angiography study of the macula and optic disc

To investigate the effects of ageing and signal strength index (SSI) on vessel density (VD) measurements of the radial peripapillary capillaries (RPC) in the optic disc, the retinal superficial (SCP) and deep (DCP) capillary plexi and the choriocapillaris (CC) of the macular area using optical coherence tomography angiography (OCT‐A) imaging.
Identification of novel biomarkers of prostate cancer through integrated analysis

Background The current methods adopted to screen for prostate cancer (PCa) can sometimes be misleading and inaccurate. Moreover, for advanced stages of PCa, the current effect of treatment is not satisfactory for some patients. Accordingly, we aimed to identify new biomarkers for the diagnosis and prognosis of PCa. Methods A series of bioinformatic tools were utilized to search for potential new biomarkers of PCa and analyze their functions, expression, clinical relevance, prognostic value, and underlying mechanisms. Results Although ASPN was overexpressed in PCa, EDN3, PENK, MEIS2, IGF1, and CXCL12 were downregulated. The univariate Cox regression analysis showed that abnormally high expression of ASPN and low expression of other genes predicted worse prognosis. Moreover, the multivariate Cox regression analysis showed that ASPN, PENK, and MEIS2 were independently associated with the overall survival (OS) of patients, whereas other markers were not. The outcomes of gene ontology and gene set enrichment analysis showed that the expression levels of these genes might be associated with cell proliferation and infiltration of immune cells in PCa. Conclusions We demonstrated that ASPN, EDN3, PENK, MEIS2, IGF1, and CXCL12 are possibly novel diagnostic indicators for PCa, whereas ASPN, PENK, and MEIS2 show appealing potential to predict the prognosis of this disease.
Mechanisms of CO Activation, Surface Oxygen Removal, Surface Carbon Hydrogenation, and C–C Coupling on the Stepped Fe(710) Surface from Computation

To understand the initial steps of Fe-based Fischer–Tropsch synthesis, systematic periodic density functional theory computations have been performed on the single-atom stepped Fe(710) surface, composed by p(3 × 3) Fe(100)-like terrace and p(3 × 1) Fe(110)-like step. It is found that CO direct dissociation into surface C and O is more favored kinetically and thermodynamically than the H-assisted activation via HCO and COH formation. Accordingly, surface O removal by hydrogen via H2O formation is the only way. On the basis of surface CHx hydrogenation (x = 0, 1, 2, 3), surface CHx + CHx coupling and CO + CHx insertion resulting in CHxCO formation followed by C–O dissociation, surface C hydrogenation toward CH3 formation is more favored kinetically than the formation of CHx-CHx and CHxCO, as well as thermodynamically. Starting from CH3, the formation of CH4 and CH3CO has similar barriers and endothermic reaction energies, while CH3CO dissociation into CH3C + O has low barrier and is highly exothermic. There.