Miracle-dz/UniFAR-FTUs huggingface dataset:
Decreased Functional Connectivity of the Primary Visual Cortex and the Correlation With Clinical Features in Patients With Intermittent Exotropia

The purpose of this study is to investigate characteristic alterations of functional connectivity (FC) patterns in the primary visual area (V1) in patients with intermittent exotropia (IXT) using resting-state functional magnetic resonance imaging (rs-fMRI) and how they relate to clinical features. Twenty-six IXT patients and 21 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent rs-fMRI. We performed FC analyses between bilateral V1 and other brain areas and compared FC strength between two groups. A Pearson correlation analysis was used to evaluate the correlation between the FC differences and clinical features. Compared with HCs, patients with IXT showed significantly lower FC of the right V1 with the right calcarine sulcus and right superior occipital gyrus, and the left V1 with right cuneus and right postcentral gyrus. The Newcastle Control Test score was positively correlated with mean FC values between the left inferior parietal lobule and bilateral V1, and between the left supramarginal gyrus and left V1. The duration of IXT was positively correlated with mean FC values between the right inferior occipital gyrus and right V1. Reduced FC between the V1 and various brain regions involved in vision and eye movement processes may be associated with the underlying neural mechanisms of impaired visual function in patients with IXT.
Intralesional Infiltrations of Cell-Free Filtrates Derived from Human Diabetic Tissues Delay the Healing Process and Recreate Diabetes Histopathological Changes in Healthy Rats

Lower limb ulcers in type-2 diabetic patients are a frequent complication that tributes to amputation and reduces survival. We hypothesized that diabetic healing impairment and other histopathologic hallmarks are mediated by a T2DM-induced tissue priming/metabolic memory that can be transferred from humans to healthy recipient animals and consequently reproduce diabetic donor’s phenotypes. We examined the effect of human T2DM tissue homogenates injected into non-diabetic rat excisional wounds. Fresh granulation tissue, popliteal artery, and peroneal nerve of patients with T2DM were obtained following amputation. Post-mammoplasty granulation and post-traumatic amputation-tissue of normal subjects acted as controls. The homogenates were intralesionally injected for 6–7 days into rats’ excisional thickness wounds. Infiltration with the different homogenates caused impaired wound closure, inflammation, nerve degeneration, and arterial thickening (all P < 0.01 vs relevant control) resembling histopathology of diabetic donor tissues. Control materials caused marginal inflammation only. Infiltration with glycated bovine albumin provoked inflammation and wound healing delay but did not induce arterial thickening. The reproduction of human diabetic traits in healthy recipient animals through a tissue homogenate support the notion on the existence of tissue metabolic memory-associated and transmissible factors, involved in the pathogenesis of diabetic complications. These may have futuristic clinical implications for medical interventions.
The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A

Protein phosphatase 2A (PP2A) activity is critical for maintaining normal physiological cellular functions. PP2A is inhibited by endogenous inhibitor proteins in several pathological conditions including cancer. A PP2A inhibitor protein, ARPP-19, has recently been connected to several human cancer types. Accordingly, the knowledge about ARPP-19—PP2A inhibition mechanism is crucial for the understanding the disease development and the therapeutic targeting of ARPP-19—PP2A. Here, we show the first structural characterization of ARPP-19, and its splice variant ARPP-16 using NMR spectroscopy, and SAXS. The results reveal that both ARPP proteins are intrinsically disordered but contain transient secondary structure elements. The interaction mechanism of ARPP-16/19 with PP2A was investigated using microscale thermophoresis and NMR spectroscopy. Our results suggest that ARPP—PP2A A-subunit interaction is mediated by linear motif and has modest affinity whereas, the interaction of ARPPs with B56-subunit is weak and transient. Like many IDPs, ARPPs are promiscuous binders that transiently interact with PP2A A- and B56 subunits using multiple interaction motifs. In summary, our results provide a good starting point for future studies and development of therapeutics that block ARPP-PP2A interactions.
The “Missing 6 dB” Revisited: Influence of Room Acoustics and Binaural Parameters on the Loudness Mismatch Between Headphones and Loudspeakers

Generations of researchers observed a mismatch between headphone and loudspeaker presentation: the sound pressure level at the eardrum generated by a headphone has to be about 6 dB higher compared to the level created by a loudspeaker that elicits the same loudness. While it has been shown that this effect vanishes if the same waveforms are generated at the eardrum in a blind comparison, the origin of the mismatch is still unclear. We present new data on the issue that systematically characterize this mismatch under variation of the stimulus frequency, presentation room, and binaural parameters of the headphone presentation. Subjects adjusted the playback level of a headphone presentation to equal loudness as loudspeaker presentation, and the levels at the eardrum were determined through appropriate transfer function measurements. Identical experiments were conducted at Oldenburg and Aachen with 40 normal-hearing subjects including 14 that passed through both sites. Our data verify a mismatch between loudspeaker and binaural headphone presentation, especially at low frequencies. This mismatch depends on the room acoustics, and on the interaural coherence in both presentation modes. It vanishes for high frequencies and broadband signals if individual differences in the sound transfer to the eardrums are accounted for. Moreover, small acoustic and non-acoustic differences in an anechoic reference environment (Oldenburg vs. Aachen) exert a large effect on the recorded loudness mismatch, whereas not such a large effect of the respective room is observed across moderately reverberant rooms at both sites. Hence, the non-conclusive findings from the literature appear to be related to the experienced disparity between headphone and loudspeaker presentation, where even small differences in (anechoic) room acoustics significantly change the response behavior of the subjects. Moreover, individual factors like loudness summation appear to be only loosely connected to the observed mismatch, i.e., no direct prediction is possible from individual binaural loudness summation to the observed mismatch. These findings – even though not completely explainable by the yet limited amount of parameter variations performed in this study – have consequences for the comparability of experiments using loudspeakers with conditions employing headphones or other ear-level hearing devices.
Personality Inventory for DSM-5 in China: Evaluation of DSM-5 and ICD-11 Trait Structure and Continuity With Personality Disorder Types

The Personality Inventory for the DSM-5 (PID-5) is an established tool for assessing personality disorder (PD) traits that was developed based on section III of the DSM-5. It is composed of 220 items, organized into 25 facets, which are distributed among five domains. The psychometric properties of the Chinese version of the PID-5 remain to be demonstrated. Two samples were embodied in this study that included 3,550 undergraduates and 406 clinical patients. To probe the structure of the PID-5, parallel analyses were conducted to explore the unidimensionality of its 25 facets and a series of confirmatory factor analyses (CFAs) were carried out to confirm the 25 lower-order facets and their distribution among five higher-order domains. Then, the PID-5 was employed to measure the DSM-5 and ICD-11 trait models and to explore the relationship of DSM-IV categorical PDs with DSM-5 and ICD-11 personality traits. Correlation and regression analyses were conducted to probe how well DSM-IV categorical PDs correspond with maladaptive personality traits specified in the DSM-5 and five ICD-11 domains. The respective average internal reliability coefficients of the 25 facets obtained for undergraduate and clinical patient samples were 0.76 and 0.81, those obtained for the five DSM-5 domains were 0.89 and 0.91, and those obtained for the five ICD-11 domains were 0.87 and 0.89. Serial CFAs confirmed the rationality of the PID-5's lower-order 25-facet structure and higher-order five-domain structure in both samples. Correlation and regression analyses showed that DSM-5 specified traits explain the variance in PD presentation with a manifold stronger correlation (R2 = 0.24–0.44) than non-specified traits (R2 = 0.04–0.12). Overall, the PID-5 was shown to be a reliable, stable, and structurally valid assessment tool that captures pathological personality traits related to DSM-5 and ICD-11 PDs.
Comprehensive Association Analysis of 21-Gene Recurrence Score and Obesity in Chinese Breast Cancer Patients

Purpose A center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients. Patients and methods Luminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status. Results Among 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P<0.05). Compared to non-overweight patients, obese ones presented significantly higher ER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all P<0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population. Conclusions RS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.
Machine Perfusion of the Liver: A Review of Clinical Trials

Although efforts have been made by transplant centers to increase the pool of available livers by extending the criteria of liver acceptance, this practice creates risks for recipients that include primary non-function of the graft, early allograft dysfunction and post-operative complications. Donor liver machine perfusion (MP) is a promising novel strategy that not only decreases cold ischemia time, but also serves as a method of assessing the viability of the graft. In this review, we summarize the data from liver machine perfusion clinical trials and discuss the various techniques available to date as well as future applications of machine perfusion. A variety of approaches have been reported including hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP); the advantages and disadvantages of each are just now beginning to be resolved. Important in this effort is developing markers of viability with lactate being the most predictive of graft functionality. The advent of machine perfusion has also permitted completely ischemia free transplantation by utilization of in situ NMP showed promising results. Animal studies that focus on defatting steatotic livers via NMP as well as groups that work on regenerating liver tissue ex vivo via MP. The broad incorporation of machine perfusion into routine clinical practice seems incredible.
Conversion of Reactive Astrocytes to Induced Neurons Enhances Neuronal Repair and Functional Recovery After Ischemic Stroke

The master neuronal transcription factor NeuroD1 can directly reprogram astrocytes into induced neurons (iNeurons) after stroke. Using viral vectors to drive ectopic ND1 expression in gliotic astrocytes after brain injury presents an autologous form of cell therapy for neurodegenerative disease. Cultured astrocytes transfected with ND1 exhibited reduced proliferation and adopted neuronal morphology within 2–3 weeks later, expressed neuronal/synaptic markers, and extended processes. Whole-cell recordings detected the firing of evoked action potentials in converted iNeurons. Focal ischemic stroke was induced in adult GFAP-Cre-Rosa-YFP mice that then received ND1 lentivirus injections into the peri-infarct region 7 days after stroke. Reprogrammed cells did not express stemness genes, while 2–6 weeks later converted cells were co-labeled with YFP (constitutively activated in astrocytes), mCherry (ND1 infection marker), and NeuN (mature neuronal marker). Approximately 66% of infected cells became NeuN-positive neurons. The majority (~80%) of converted cells expressed the vascular glutamate transporter (vGLUT) of glutamatergic neurons. ND1 treatment reduced astrogliosis, and some iNeurons located/survived inside of the savaged ischemic core. Western blotting detected higher levels of BDNF, FGF, and PSD-95 in ND1-treated mice. MultiElectrode Array (MEA) recordings in brain slices revealed that the ND1-induced reprogramming restored interrupted cortical circuits and synaptic plasticity. Furthermore, ND1 treatment significantly improved locomotor, sensorimotor, and psychological functions. Thus, conversion of endogenous astrocytes to neurons represents a plausible, on-site regenerative therapy for stroke.
Complete Blood Count Score Model Predicts Inferior Prognosis in Primary Central Nervous System Lymphoma

Background Primary central nervous system lymphoma (PCNSL), an aggressive type of non-Hodgkin lymphoma, has a poor prognosis. Currently available prognostic scoring systems are inadequate. We therefore aimed to investigate the predictive values of complete blood counts (CBCs) in PCNSL. Materials and Methods The cohort of this retrospective study comprised 73 PCNSL patients. The predictive values of selected CBCs, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI), were analyzed. Results Ages and Memorial Sloan Kettering Cancer Center (MSKCC) scores of PCNSL patients correlated with NLR, PLR, and SII values (p <0.05). Both age and MSKCC scores correlated with inferior progression-free survival (PFS) and overall survival (OS) (p <0.05). High NLR, PLR, SII, and SIRI were significant predictors of shorter PFS and OS (p <0.05). NLR, PLR, SII, and SIRI were integrated to generate a “CBC score” model that accurately stratified PCNSL patients into three risk groups. The median PFS for low-risk, intermediate-risk, and high-risk groups were 24 ((12.458–35.542), 17 (10.626–23.374), and 9 (8.893–19.107) months, respectively (p = 0.011), and the median OS were 33 (19.175–46.825), 18 (16.368–19.632), and 9 (6.521–11.479) months, respectively (p = 0.008). Multivariate Cox regression model showed that MSKCC score (hazard ratio (HR) = 3.791, p <0.001), PLR (HR = 1.003, p = 0.013), and CBC score (HR = 1.873, p = 0.011) were independent predictors for PFS, whereas MSKCC score (HR = 4.128, p <0.001), PLR (HR = 1.003, p = 0.005), and CBC score (HR = 1.907, p = 0.004) were independent predictors for OS. Conclusion The CBC score model may be a promising predictive system for PCNSL patients.
Memristor Based Binary Convolutional Neural Network Architecture With Configurable Neurons

The memristor-based convolutional neural network (CNN) gives full play to the advantages of memristive devices, such as low power consumption, high integration density, and strong network recognition capability. Consequently, it is very suitable for building a wearable embedded application system and has broad application prospects in image classification, speech recognition, and other fields. However, limited by the manufacturing process of memristive devices, high-precision weight devices are currently difficult to be applied in large-scale. In the same time, high-precision neuron activation function also further increases the complexity of network hardware implementation. In response to this, this paper proposes a configurable full-binary convolutional neural network (CFB-CNN) architecture, whose inputs, weights, and neurons are all binary values. The neurons are proportionally configured to two modes for different non-ideal situations. The architecture performance is verified based on the MNIST data set, and the influence of device yield and resistance fluctuations under different neuron configurations on network performance is also analyzed. The results show that the recognition accuracy of the 2-layer network is about 98.2%. When the yield rate is about 64% and the hidden neuron mode is configured as −1 and +1, namely ±1 MD, the CFB-CNN architecture achieves about 91.28% recognition accuracy. Whereas the resistance variation is about 26% and the hidden neuron mode configuration is 0 and 1, namely 01 MD, the CFB-CNN architecture gains about 93.43% recognition accuracy. Furthermore, memristors have been demonstrated as one of the most promising devices in neuromorphic computing for its synaptic plasticity. Therefore, the CFB-CNN architecture based on memristor is SNN-compatible, which is verified using the number of pulses to encode pixel values in this paper.
Pegylated Liposomal Doxorubicin in Vindesine-Based and Bortezomib-Based Regimens for Patients With Newly Diagnosed Multiple Myeloma: A Retrospective Study of Efficacy and Safety

Purpose Although pegylated liposomal doxorubicin (PLD) has been approved in combination with bortezomib for relapsed/refractory multiple myeloma (MM), the antitumor efficacy and tolerability of PLD in different regimens for patients with newly diagnosed MM (NDMM) have not been fully defined. Methods A total of 249 NDMM patients diagnosed between January 2008 and October 2019 were included in this retrospective study. Among them, 112 patients received vindesine-based chemotherapy (35 vDD and 77 vAD) and 137 received bortezomib-based chemotherapy (58 VDD and 79 VD). Results In bortezomib-containing regimens, the complete response rate (48.3 vs. 30.4%, p = 0.033) and very good partial response or better rate (74.1 vs. 57.0%, p = 0.038) of VDD were significantly higher than those of VD subgroup. While no superior survival was found between VDD and VD subgroup. In vindesine-containing regimens, no statistical significance was identified between vDD and vAD in terms of response rate and survival. The occurrence rates of all cardiac AEs were similar between VDD and VD. Conclusions The vDD regimen was similar with vAD in the aspect of response rate, survival, and toxicity in NDMM patients. The addition of PLD to VD brought deeper response without increased toxicity, while no superior survival was found.
EZH2 Inhibition Interferes With the Activation of Type I Interferon Signaling Pathway and Ameliorates Lupus Nephritis in NZB/NZW F1 Mice

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase mediating trimethylation of H3K27, which represses gene expression and is critical to immune regulation. Inhibition of EZH2 is proved to have the potential of treating many diseases. However, whether inhibition of EZH2 affects type I interferon (IFN-I) signaling pathway, the abnormality of which is an important pathogenic mechanism for SLE, is still elusive. Here, we report, unexpectedly, a positive regulatory function of EZH2 in IFN-I signaling pathway, which contributes to the overactivation of IFN-I signaling pathway in SLE. We show that the expression of EZH2 was upregulated and positively correlated with the overexpression of interferon stimulated genes (ISGs) in both peripheral blood mononuclear cells and renal tissues of SLE patients. In vitro inhibition of EZH2 by either siRNAs or chemical inhibitors reduced the phosphorylation of STAT1 and the induction of ISGs stimulated by IFN-I. Additionally, inhibition of EZH2 interfered with the in vivo and ex vivo activation of IFN-I signaling pathway elicited by intravenous injection of adenovirus vector expressing mouse IFN-α5 and exogeneous stimulation with IFN-α, respectively. We evaluated the therapeutic effects of EZH2 inhibitor in NZB/NZW F1 mice which depend on IFN-I signaling pathway for the lupus-like disease development. Administration of EZH2 inhibitor prolonged the survival, reduced the levels of anti-dsDNA autoantibodies, and improved lupus nephritis of the mice. What’s more, EZH2 inhibitor attenuated the expression of ISGs in the kidneys of these mice. In summary, we show that excessive EZH2 contributes to the overactivation of IFN-I signaling pathway in SLE. EZH2 inhibitor has the potential to inhibit IFN-I signaling pathway and alleviate lupus nephritis. Additionally, diverse disease driving pathways exist among systemic lupus erythematosus (SLE) patient, and even in the same patients. Common regulators of different pathogenic pathways can be multivalent therapeutic targets. Together with previous studies showing EZH2 is involved in T-cell and B-cell mediated immune responses, EZH2 could be a potent multivalent therapeutic target for SLE.
FORMS OF PHOSPHORUS IN SOME IMPORTANT AGRICULTURAL SOILS OF NIGERIA

The phosphorus status of twenty-one selected soils from various parts of Nigeria was studied. Total P content in the surface soils studied ranged widely from 120 to 1880 ppm. In most cases, the relative abundance of the various fractions of inorganic P was in the order of occluded P ≫ Fe-P > Al-P ≥ Ca-P. The distribution of various P forms was related to the parent material, degree of weathering, and drainage conditions of the soils. Organic P constituted more than half of the total P in most of the forest soils. Multiple correlation showed that organic P content was significantly correlated with soil pH, organic carbon content and total P content in the soils.