Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic brain activity reorganization contributes to long-term compensation of higher-order hearing abilities in single-sided deafness

Single-sided deafness (SSD) is an extreme case of partial hearing deprivation and results in a significant decline in higher-order hearing abilities, including sound localization and speech-in-noise recognition. Clinical studies have reported that patients with SSD recover from these higher-order hearing abilities to some extent over time. Neuroimaging studies have observed extensive brain functional plasticity in patients with SSD. However, studies investigating the role of plasticity in functional compensation, particularly those investigating the relationship between intrinsic brain activity alterations and higher-order hearing abilities, are still limited. In this study, we used resting-state functional MRI to investigate intrinsic brain activity, measured by the amplitude of low-frequency fluctuation (ALFF), in 19 patients with left SSD, 17 patients with right SSD, and 21 normal hearing controls (NHs). All patients with SSD had durations of deafness longer than 2 years. Decreased ALFF values in the bilateral precuneus (PCUN), lingual gyrus, and left middle frontal gyrus were observed in patients with SSD compared with the values of NHs. Longer durations of deafness were correlated with better hearing abilities, as well as higher ALFF values in the left inferior parietal lobule, the angular gyrus, the middle occipital gyrus, the bilateral PCUN, and the posterior cingulate gyrus. Moreover, we observed a generally consistent trend of correlation between ALFF values and higher-order hearing abilities in specific brain areas in patients with SSD. That is, better abilities were correlated with lower ALFF values in the frontal regions and higher ALFF values in the PCUN and surrounding parietal-occipital areas. Furthermore, mediation analysis revealed that the ALFF values in the PCUN were a significant mediator of the relationship between the duration of deafness and higher-order hearing abilities. Our study reveals significant plasticity of intrinsic brain activity in patients with SSD and suggests that reorganization of intrinsic brain activity may be one of the compensatory mechanisms that facilitate improvement in higher-order hearing abilities in these patients over time.
The molecular, immune features, and risk score construction of intraductal papillary mucinous neoplasm patients

Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic precancerous lesion, with increasing incidence in recent years. However, the mechanisms of IPMN progression into invasive cancer remain unclear. The mRNA expression data of IPMN/PAAD patients were extracted from the TCGA and GEO databases. First, based on GSE19650, we analyzed the molecular alterations, tumor stemness, immune landscape, and transcriptional regulation of IPMN progression. The results indicated that gene expression changed dramatically, specifically at the intraductal papillary-mucinous adenoma (IPMA) stage. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Kyoto Encyclopedia of Genes and Genomes (GSEA) pathway analyses showed that glycoprotein-related, cell cycle, and P53 pathways displayed the most significant changes during progression. With IPMN progression, tumor stemness increased continuously, and KRAS, ERBB3, RUNX1, and ELF3 are essential driver genes affecting tumor stemness. Motif analysis suggested that KLF4 may be a specific transcription factor that regulates gene expression in the IPMA stage, while MYB and MYBL1 control gene expression in the IPMC and invasive stages, respectively. Then, GSE19650 and GSE71729 transcriptome data were combined to perform the least absolute shrinkage and selection operator (LASSO) method and Cox regression analysis to develop an 11-gene prediction model (KCNK1, FHL2, LAMC2, CDCA7, GPX3, C7, VIP, HBA1, BTG2, MT1E, and LYVE1) to predict the prognosis of pancreatic cancer patients. The reliability of the model was validated in the GSE71729 and TCGA databases. Finally, 11 additional IPMN patients treated in our hospital were included, and the immune microenvironment changes during IPMN progression were analyzed by immunohistochemistry (IHC). IHC results suggest that Myeloid-derived suppressor cells (MDSCs) and macrophages may be key in the formation of immunosuppressive microenvironment of IPMN progression. Our study deepens our understanding of IPMN progression, especially the changes in the immune microenvironment. The findings of this work may contribute to the development of new therapeutic strategies for IPMN.
The influence of signs of social class on compassionate responses to people in need

A field experiment (N = 4,536) examined how signs of social class influence compassionate responses to those in need. Pedestrians in two major cities in the United States were exposed to a confederate wearing symbols of relatively high or low social class who was requesting money to help the homeless. Compassionate responding was assessed by measuring the donation amount of the pedestrians walking past the target. Pedestrians gave more than twice (2.55 times) as much money to the confederate wearing higher-class symbols than they did to the one wearing lower-class symbols. A follow-up study (N = 504) exposed participants to images of the target wearing the same higher- or lower-class symbols and examined the antecedents of compassionate responding. Consistent with theorizing, higher-class symbols elicited perceptions of elevated competence, trustworthiness, similarity to the self, and perceived humanity compared to lower-class symbols. These results indicate that visible signs of social class influence judgments of others’ traits and attributes, as well as in decisions to respond compassionately to the needs of those who are suffering.
Word frequency effects found in free recall are rather due to Bayesian surprise

The inconsistent relation between word frequency and free recall performance (sometimes a positive one, sometimes a negative one, and sometimes no relation) and the non-monotonic relation found between the two cannot all be explained by current theories. We propose a theoretical framework that can explain all extant results. Based on an ecological psychology analysis of the free recall situation in terms of environmental and informational resources available to the participants, we propose that because participants’ cognitive system has been shaped by their native language, free recall performance is best understood as the end result of relational properties that preexist the experimental situation and of the way the words from the experimental list interact with those. In addition to this, we borrow from predictive coding theory the idea that the brain constantly predicts “what is coming next” so that it is mainly prediction errors that will propagate information forward. Our ecological psychology analysis indicates there will be “prediction errors” because the word frequency distribution in an experimental word list is inevitably different from the particular Zipf’s law distribution of the words in the language that shaped participants’ brains. We further propose the particular distributional discrepancies inherent to a given word list will trigger, as a function of the words that are included in the list, their order, and of the words that are absent from the list, a surprisal signal in the brain, something that is isomorphic to the concept of Bayesian surprise. The precise moment when Bayesian surprise is triggered will determine to what word of the list that Bayesian surprise will be associated with, and the word the Bayesian surprise will be associated with will benefit from it and become more memorable as a direct function of the magnitude of the surprisal. Two experiments are presented that show a proxy of Bayesian surprise explains the free recall performance and that no effect of word frequency is found above and beyond the effect of that proxy variable. We then discuss how our view can account for all data extant in the literature on the effect of word frequency on free recall.
A higher spectral range of beetle bioluminescence with infraluciferin

Coleopteran bioluminescence is unique in that beetle luciferases emit colors ranging between green (ca.550 nm) and red (ca.600 nm), including intermediate colors such as yellow and orange, allowing up to 3 simultaneous parameters to be resolved in vitro with natural luciferin (D-LH2). Here, we report a more than doubling of the maximum bioluminescence wavelength range using a single synthetic substrate, infraluciferin (iLH2). We report that different luciferases can emit colors ranging from visible green to near-infrared (nIR) with iLH2, including in human cells. iLH2 was designed for dual color far-red to nIR bioluminescence imaging (BLI) in small animals and has been utilized in different mouse models of cancer (including a metastatic hepatic model showing detailed hepatic morphology) and for robust dual parameter imaging in vivo (including in systemic hematological models). Here, we report the properties of different enzymes with iLH2: Lampyrid wild-type (WT) Photinus pyralis (Ppy) firefly luciferase, Ppy-based derivatives previously engineered to be thermostable with D-LH2, and also color-shifted Elaterid-based enzymes: blue-shifted Pyrearinus termitilluminans derivative Eluc (reported D-LH2 λmax = 538 nm) and red-shifted Pyrophorus plagiopthalamus derivative click beetle red (CBR) luciferase (D-LH2 λmax = 618 nm). As purified enzyme, in bacteria or in human cells, Eluc emitted green light (λmax = 536 nm) with DL-iLH2 whereas Ppy Fluc (λmax = 689 nm), x2 Fluc (λmax = 704 nm), x5 Fluc (λmax = 694 nm), x11 Fluc (λmax = 694 nm) and CBR (λmax = 721 nm) produced far-red to nIR peak wavelengths. Therefore, with iLH2, enzyme λmaxes can be separated by ca.185nm, giving almost non-overlapping spectra. This is the first report of single-substrate bioluminescence color emission ranging from visible green to nIR in cells and may help shed light on the color tuning mechanism of beetle luciferases. We also report on the reason for the improvement in activity of x11 Fluc with iLH2 and engineer an improved infraluciferase (iluc) based on this mutant.
Barriers to hydroxyurea use from the perspectives of providers, individuals with sickle cell disease, and families: Report from a U.S. regional collaborative

Sickle cell disease (SCD) is an inherited blood disorder that affects about 100,000 people in the U.S., primarily Blacks/African-Americans. A multitude of complications negatively impacts quality of life. Hydroxyurea has been FDA approved since 1998 as a disease-modifying therapy for SCD, but is underutilized. Negative and uninformed perceptions of hydroxyurea and barriers to its use hinder adherence and promotion of the medication. As the largest real-world study to date that assessed hydroxyurea use for children and adults with SCD, we gathered and analyzed perspectives of providers, individuals with SCD, and families. Participants provided information about socio-demographics, hospital and emergency admissions for pain, number of severe pain episodes interfering with daily activities, medication adherence, and barriers to hydroxyurea. Providers reported on indications for hydroxyurea, reasons not prescribed, and current laboratory values. We found that hydroxyurea use was reported in over half of eligible patients from this large geographic region in the U.S., representing a range of sickle cell specialty clinical settings and practices. Provider and patient/caregiver reports about hydroxyurea use were consistent with one another; adults 26 years and older were least likely to be on hydroxyurea; and the likelihood of being on hydroxyurea decreased with one or more barriers. Using the intentional and unintentional medication nonadherence framework, we found that, even for patients on hydroxyurea, challenges to taking the medicine at the right time and forgetting were crucial unintentional barriers to adherence. Intentional barriers such as worry about side effects and “tried and it did not work” were important barriers for young adults and adults. For providers, diagnoses other than HgbSS or HgbS-β0 thalassemia were associated with lower odds of prescribing, consistent with evidence-based guidelines. Our results support strengthening provider understanding and confidence in implementing existing SCD guidelines, and the importance of shared decision making. Our findings can assist providers in understanding choices and decisions of families; guide individualized clinical discussions regarding hydroxyurea therapy; and help with developing tailored interventions to address barriers. Addressing barriers to hydroxyurea use can inform strategies to minimize similar barriers in the use of emerging and combination therapies for SCD.
Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells

The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment.
Chronic tobacco smoking, impaired reward-based decision-making, and role of insular cortex: A comparison between early-onset smokers and late-onset smokers

Introduction The literature suggests that tobacco smoking may have a neurotoxic effect on the developing adolescent brain. Particularly, it may impair the decision-making process of early-onset smokers (<16 years), by rendering them more prone to impulsive and risky choices toward rewards, and therefore more prone to smoking relapses, in comparison to late-onset smokers (≥16 years). However, no study has ever investigated reward-based decision-making and structural brain differences between early-onset smokers and late-onset smokers. Methods Computerized measures of reward-based decision-making [Cambridge Gambling Task (CGT); 5-trials adjusting delay discounting task (ADT-5)] were administered to 11 early-onset smokers (mean age at regular smoking initiation = 13.2 years), 17 late-onset smokers (mean age at regular smoking initiation = 18.0 years), and 24 non-smoker controls. Voxel-based morphometry (VBM) was utilized to investigate the gray matter (GM) and white matter (WM) volume differences in fronto-cortical and striatal brain regions between early-onset smokers, late-onset smokers, and non-smokers. Results Early-onset smokers displayed a riskier decision-making behavior in comparison to non-smokers as assessed by the CGT (p < 0.01, Cohen’s f = 0.48). However, no significant differences (p > 0.05) in reward-based decision-making were detected between early-onset smokers and late-onset smokers. VBM results revealed early-onset smokers to present lower GM volume in the bilateral anterior insular cortex (AI) in comparison to late-onset smokers and lower WM volume in the right AI in comparison to late-onset smokers. Conclusion Impairments in reward-based decision-making may not be affected by tobacco smoking initiation during early adolescence. Instead, lower GM and WM volume in the AI of early-onset smokers may underline a vulnerability to develop compulsive tobacco seeking and smoking behavior during adulthood.
Vertically layered flow structure at confluence of a reservoir and tributary carrying high sediment loads

Enhanced understanding of flow structure at a river confluence is essential for predictions of sediment transport and morphological evolution. To date, however, the confluent flow structure of a reservoir and tributary carrying high sediment loads has remained poorly understood, and may be vertically layered sharply, featuring subaqueous sediment-laden flow, i.e., turbidity currents underneath subaerial clear water. Here a recently established 2D double layer-averaged model, able to resolve the formation, propagation, and recession of turbidity currents, is used to investigate a series of idealized laboratory-scale cases and a prototype case study of the Guxian Reservoir on the Yellow River, China. Four primary patterns of the stable, vertically layered flow structure at a reservoir-tributary confluence are identified: 1) single layers of sediment-laden inflow in both the main channel and tributary, sustained by sufficient vertical mixing; 2) a double layer in the main channel and a single layer of sediment-laden inflow in the tributary, when the sediment-laden flow in the tributary suffices to block intrusion of flow in the main channel; 3) a single layer of sediment-laden inflow in the main channel and a double layer in the tributary, induced by the intrusion of sediment-laden flow from the main channel into clear-water flow with small discharge in the tributary; and 4) double layers in both the main channel and tributary, which may be further divided into three subpatterns, as turbidity current exists in both the main channel and tributary, or in the main channel (tributary) intruding into the tributary (main channel). In response to unsteady discharge and sediment inputs from upstream, the vertically layered flow structure evolves in time, and may fall into one of the patterns identified above. Although bed deformation in the long term may modify the confluent flow, the vertically layered flow pattern remains so far as the present cases are concerned. The findings have implications for sediment transport and morphological evolution at a reservoir–tributary confluence, for which further studies are suggested to inform the optimization of reservoir operation schemes to mitigate capacity loss caused by sedimentation.
A zona incerta-basomedial amygdala circuit modulates aversive expectation in emotional stress-induced aversive learning deficits

A previously published study showed that stress may interfere with associative aversive learning and facilitate mood-related disorders. However, whether emotional stress alone affects aversive learning is unknown. Using three chamber-vicarious social defeat stress (3C-VSDS) model mice, we investigated the effect of emotional stress on aversive learning. An important origin of dopamine (DA) neurons, the zona incerta (ZI), is expected to be a novel target for the modulation of aversive learning. However, less is known about the circuit mechanism of ZIDA neurons in aversive learning. Here, we subjected mice to a fear-conditioning system (FCS) and observed an increased calcium activity of ZI TH+ neurons in aversive expectation during the conditioning phase, especially during the late stage of the conditional stimulus (CS) when CS and unconditional stimulus (US) pairings were used. Optogenetic inhibition of ZI TH+ neurons at the late stage of CS disrupted conditioned fear learning in mice. We further identified a TH+ projection from the ZI to the basomedial amygdala (BMA) and found that optogenetic inhibition of the ZI-BMA circuit could also block aversive learning. Finally, we used 3C-VSDS mice as a model of emotional stress. We found that the 3C-VSDS model mice demonstrated reduced aversive expectation associated with ZI TH+ neurons in the late stage of CS and impaired aversive learning in FCS. Optogenetic activation of ZI-BMA TH+ projections in the late stage of CS significantly reversed the aversive FCS learning disability of 3C-VSDS model mice. These data suggest that a TH+ circuit from the ZI to the BMA is required for aversive expectation, both at baseline and in 3C-VSDS-induced aversive learning deficits and that this circuit is a potential target for the modulation of aversive learning. Low activity of ZI-BMA TH+ projections is one reason for 3C-VSDS-induced aversive learning deficits.
A stepwise strategy integrating metabolomics and pseudotargeted spectrum–effect relationship to elucidate the potential hepatotoxic components in Polygonum multiflorum

Polygonum multiflorum (PM) Thunb. , a typical Chinese herbal medicine with different therapeutic effect in raw and processed forms, has been used worldwide for thousands of years. However, hepatotoxicity caused by PM has raised considerable concern in recent decades. The exploration of toxic components in PM has been a great challenge for a long time. In this study, we developed a stepwise strategy integrating metabolomics and pseudotargeted spectrum–effect relationship to illuminate the potential hepatotoxic components in PM. First, 112 components were tentatively identified using ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS). Second, based on the theory of toxicity attenuation after processing, we combined the UPLC-Q-TOF-MS method and plant metabolomics to screen out the reduced differential components in PM between raw and processed PM. Third, the proposed pseudotargeted MS of 16 differential components was established and applied to 50 batches of PM for quantitative analysis. Fourth, the hepatocytotoxicity of 50 batches of PM was investigated on two hepatocytes, LO2 and HepG2. Last, three mathematical models, gray relational analysis, orthogonal partial least squares analysis, and back propagation artificial neural network, were established to further identify the key variables affecting hepatotoxicity in PM by combining quantitative spectral information with toxicity to hepatocytes of 50 batches of PM. The results suggested that 16 components may have different degrees of hepatotoxicity, which may lead to hepatotoxicity through synergistic effects. Three components (emodin dianthrones, emodin-8-O-β-D-glucopyranoside, PM 14-17) were screened to have significant hepatotoxicity and could be used as toxicity markers in PM as well as for further studies on the mechanism of toxicity. Above all, the study established an effective strategy to explore the hepatotoxic material basis in PM but also provides reference information for in-depth investigations on the hepatotoxicity of PM.