Miracle-dz/UniFAR-FTUs huggingface dataset:
Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder and the most common cause of dementia in the elderly. The presence of large numbers of senile plaques, neurofibrillary tangles, and cerebral atrophy is the characteristic feature of AD. Amyloid β peptide (Aβ), derived from the amyloid precursor protein (APP), is the main component of senile plaques. AD has been extensively studied using methods involving cell lines, primary cultures of neural cells, and animal models; however, discrepancies have been observed between these methods. Dissociated cultures lose the brain’s tissue architecture, including neural circuits, glial cells, and extracellular matrix. Experiments with animal models are lengthy and require laborious monitoring of multiple parameters. Therefore, it is necessary to combine these experimental models to understand the pathology of AD. An experimental platform amenable to continuous observation and experimental manipulation is required to analyze long-term neuronal development, plasticity, and progressive neurodegenerative diseases. In the current study, we provide a practical method to slice and cultivate rodent hippocampus to investigate the cleavage of APP and secretion of Aβ in an ex vivo model. Furthermore, we provide basic information on Aβ secretion using slice cultures. Using our optimized method, dozens to hundreds of long-term stable slice cultures can be coordinated simultaneously. Our findings are valuable for analyses of AD mouse models and senile plaque formation culture models.
Analysis of safety and efficacy of conservative treatment and endovascular treatment in patients with spontaneous isolated mesenteric artery dissection

Background Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare disease with abdominal pain as the main clinical manifestation, but its optimal treatment strategy has not yet been determined. Based on this, this study explored a safe and effective treatment method by analyzing and comparing the safety and efficacy of conservative treatment and endovascular treatment in SISMAD patients. Methods The clinical and imaging data and treatment effects of 85 patients with SISMAD who were admitted to the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to December 2020 were retrospectively analyzed. Two groups were treated, the data of patients in conservative treatment group and endovascular treatment group were analyzed, and a safe and effective treatment method for SISMAD was discussed. Results The mean follow-up time was 36.58 ± 25.03 months. The success rate of interventional operation was 86.11% (31/36), and the operation failed because the guide wire could not enter the true lumen in four cases. One case was terminated due to poor physical condition of the patient who could not tolerate surgery. There were no significant differences in gender, body mass index, clinical manifestations, and past history between conservative treatment and endovascular treatment (P > 0.05), but in age, superior mesenteric artery-distal aorta angle, distance from the superior mesenteric artery opening to dissection, dissection length, and true lumen stenosis. There was a statistical difference between the two groups in the rate and Yun classification (P < 0.05). Conclusions Conservative treatment is effective for most symptomatic SISMAD patients, and close monitoring is required; for patients with persistent symptoms and severe true lumen stenosis (especially Yun classification type III), endovascular treatment is preferred; endovascular treatment is mainly based on endovascular bare stent placement. Patients receiving stent implantation may suffer from stent stenosis or occlusion in the long term, and most of them have no obvious symptoms of intestinal ischemia; the prognosis is good.
Dysmenorrhea catastrophizing and functional impairment in female pelvic pain

Background Dysmenorrhea is suggested to increase the risk of chronic pain by enhancing central sensitization. However, little is known about whether emotional and cognitive responses induced by dysmenorrhea contribute to chronic pain interference. This study examined the association between catastrophizing specific to dysmenorrhea and both dysmenorrhea and chronic pelvic pain (CPP)-associated pain interference. Methods Women (N = 104) receiving care for CPP through a tertiary gynecological pain clinic between 2017 and 2020 were recruited. They completed the Pain Catastrophizing Scale, the Brief Pain Inventory–pain interference, and a separate questionnaire regarding dysmenorrhea symptoms and treatment preceding the development of CPP. Dysmenorrhea catastrophizing and interference measures were developed and tested for internal consistency and construct validity. Multiple linear regression models examined dysmenorrhea catastrophizing in association with dysmenorrhea interference and CPP-associated pain interference. Results Dysmenorrhea catastrophizing and interference measures demonstrated excellent internal consistency (Cronbach's Alpha = 0.93 and 0.92 respectively) and evidence of construct validity (correlated with dysmenorrhea severity and treatment, Ps < 0.01). Dysmenorrhea catastrophizing was moderately correlated with pain catastrophizing (ρ = 0.30, P = 0.003), and was associated with greater dysmenorrhea interference (P < 0.001) and CPP-associated pain interference (P = 0.032) accounting for general pain catastrophizing and other outcome-specific confounders. Dysmenorrhea intensity was most predictive of dysmenorrhea catastrophizing. Conclusion Among our clinical sample of women with CPP, dysmenorrhea catastrophizing was associated with greater dysmenorrhea interference and subsequent CPP-associated pain interference. More research is needed to determine whether reduction in dysmenorrhea catastrophizing leads to reduced pain interference associated with female pelvic pain.
MePAL6 regulates lignin accumulation to shape cassava resistance against two-spotted spider mite

Introduction The two-spotted spider mite (TSSM) is a devastating pest of cassava production in China. Lignin is considered as an important defensive barrier against pests and diseases, several genes participate in lignin biosynthesis, however, how these genes modulate lignin accumulation in cassava and shape TSSM-resistance is largely unknown. Methods To fill this knowledge gap, while under TSSM infestation, the cassava lignin biosynthesis related genes were subjected to expression pattern analysis followed by family identification, and genes with significant induction were used for further function exploration. Results Most genes involved in lignin biosynthesis were up-regulated when the mite-resistant cassava cultivars were infested by TSSM, noticeably, the MePAL gene presented the most vigorous induction among these genes. Therefore, we paid more attention to dissect the function of MePAL gene during cassava-TSSM interaction. Gene family identification showed that there are 6 MePAL members identified in cassava genome, further phylogenetic analysis, gene duplication, cis-elements and conserved motif prediction speculated that these genes may probably contribute to biotic stress responses in cassava. The transcription profile of the 6 MePAL genes in TSSM-resistant cassava cultivar SC9 indicated a universal up-regulation pattern. To further elucidate the potential correlation between MePAL expression and TSSM-resistance, the most strongly induced gene MePAL6 were silenced using virus-induced gene silencing (VIGS) assay, we found that silencing of MePAL6 in SC9 not only simultaneously suppressed the expression of other lignin biosynthesis genes such as 4-coumarate--CoA ligase (4CL), hydroxycinnamoyltransferase (HCT) and cinnamoyl-CoA reductase (CCR), but also resulted in decrease of lignin content. Ultimately, the suppression of MePAL6 in SC9 can lead to significant deterioration of TSSM-resistance. Discussion This study accurately identified MePAL6 as critical genes in conferring cassava resistance to TSSM, which could be considered as promising marker gene for evaluating cassava resistance to insect pest.
Dependence of frequency of convective cloud occurrence on the orbital drift of satellites

Deriving accurate time‐series of cloud cover from satellite sensor data still remains a challenging task. The instruments onboard polar orbiting NOAA satellites offer the opportunity to prepare cloud climatology on a global scale; however, the orbital drifts of these satellites can introduce uncertainty when deriving such cloud climatology. The aim of this letter is to point out the importance and to estimate the impact of orbital drift on long‐term time‐series of the observation of convective cloud frequency of occurrence. The 20 years of daytime AVHRR data from over the Indian subcontinent for the summer monsoon season is used in this study. All four AVHRRs onboard NOAA‐7, ‐9, ‐11, and ‐14 satellites show positive correlation between increased cloud frequency and the delay in equator crossing‐times during their lifetime. This increase is significant over land, but over the ocean, there is no discernible effect. This effect should be considered to avoid spurious trends in cloud cover. Further in‐depth investigations are needed to make possible corrections.
Room-temperature atmospheric pressure plasma plume for biomedical applications

As low-temperature nonequilibrium plasmas come to play an increasing role in biomedical applications, reliable and user-friendly sources need to be developed. These plasma sources have to meet stringent requirements such as low temperature (at or near room temperature), no risk of arcing, operation at atmospheric pressure, preferably hand-held operation, low concentration of ozone generation, etc. In this letter, we present a device that meets exactly such requirements. This device is capable of generating a cold plasma plume several centimeters in length. It exhibits low power requirements as shown by its current-voltage characteristics. Using helium as a carrier gas, very little ozone is generated and the gas temperature, as measured by emission spectroscopy, remains at room temperature even after hours of operations. The plasma plume can be touched by bare hands and can be directed manually by a user to come in contact with delicate objects and materials including skin and dental gum without causing any heating or painful sensation.
Precoloring extension for K 4 -minor-free graphs

Let G=(V, E) be a graph where every vertex v∈V is assigned a list of available colors L(v). We say that G is list colorable for a given list assignment if we can color every vertex using its list such that adjacent vertices get different colors. If L(v)=l1, …, kr for all v∈V then a corresponding list coloring is nothing other than an ordinary k-coloring of G. Assume that W⊆V is a subset of V such that G[W] is bipartite and each component of G[W] is precolored with two colors taken from a set of four. The minimum distance between the components of G[W] is denoted by d(W). We will show that if G is K4-minor-free and d(W)≥7, then such a precoloring of W can be extended to a 4-coloring of all of V. This result clarifies a question posed in 10. Moreover, we will show that such a precoloring is extendable to a list coloring of G for outerplanar graphs, provided that |L(v)|=4 for all v∈VbW and d(W)≥7. In both cases the bound for d(W) is best possible. © 2009 Wiley Periodicals, Inc. J Graph Theory 60: 284-294, 2009
Immunomorphogenesis in Degenerative Disc Disease: The Role of Proinflammatory Cytokines and Angiogenesis Factors

Back pain (BP) due to degenerative spinal injury is a severe, often disabling disease and it tends to decrease age of onset. The cellular and molecular basis of the disc and adjacent structures degradation remains in the focus of pathophysiologists and pathomorphologists close attention. The aim of the study was to determine the expression level of proinflammatory cytokines (IL-1{beta}, IL-6, IL-17) and angiogenesis markers (VEGF-A and CD31) in intervertebral disc (IVD) tissue, their association between each other and between disc degeneration in young people with discogenic BP. In patients who underwent discectomy for a disc herniation, a clinical examination, magnetic resonance imaging (MRI) of the lumbar spine, histological and immunohistochemical analyses of these factors in the disc tissue were performed in comparison with the parameters of healthy group samples (controls). Histology image analysis of IVD fragments of the degenerative disc disease (DDD) group detected zones of inflammatory infiltration, combined with vascularization, the presence of granulation tissue and clusters of chondrocytes in the tissue of nucleus pulposus (NP). Statistically significant expression of IL-1{beta}, IL-6, IL-17 and VEGF-A (especially on the chondrocytes surface) and CD31 (in the disc matrix) was evident in the samples of the DDD group compared with the controls (p < 0.0001), that showed a strong correlation with the histological disc degeneration stage (r > 0.5; p < 0.0001). This denotes a high immunoinflammatory potential of chondrocytes and demonstrates their altered morphogenetic properties. The coincidence of the spatial expression of IL-1{beta} and IL-17 in the perivascular zone endothelium and in the vascular lumen (p < 0.01) was found, which point at the inflammatory synergy of these cytokines. High expression of VEGF-A prevailed on the surface of chondrocytes in cell clusters compared to the matrix (p < 0.0001), indicating that the NP cells trigger the angiogenesis. The absence of CD31 in the cracks of NP with high expression in the disc matrix states the secondary nature of IVD defects due to degeneration, and not due to vascular ingrowth. A high number of patients with Modic changes according to MRI data shown the contribution of cytokines to the formation of reactive spondylitis and the clinical course of BP. These results obtained will help to development molecular/cellular targets and basic strategies for therapy of BP with DDD in the early stages in young people.
Predicting ward transfer mortality with machine learning

Background: Predicting mortality and morbidity amongst hospitalized patients has long been a struggle for inpatient Internal Medicine physicians. To prevent physician burnout, hospital organizations are turning to shift work for the care of hospitalized patients. Such shift work frequently leads to a handoff of patients, with many physicians often being the sole provider in the hospital for close to one hundred patients. Objectives: We propose developing an artificial intelligence model that helps predict which patients will be most at risk of increased mortality. This model would assist providers and frontline staff in focusing their efforts on improving patient outcomes. Materials and Methods: Records of patients who were transferred from non-intensive care units to intensive care units were queried from the Veteran Affairs Corporate Data Warehouse (CDW). Two thousand four hundred twenty-five records were identified. The patient outcome was designated a dependent variable, with bad outcome defined as the patient dying within 30 days of admission and good outcome as the patient being alive within 30 days of admission. Using twenty-two independent variables, we trained sixteen machine learning models, of which six best-performing ones were fine-tuned and evaluated on the testing dataset. Finally, we repeated this process with twenty independent variables, omitting the Length of Stay and Days to Intensive Care Unit Transfer variables which are unknown at the time of admission. Results: The best results were obtained with the LightGBM model with both datasets, one that included Length of Stay and Days to Intensive Care Unit Transfer variables and the other without these two variables. The former achieved Receiver Operating Characteristics Curve - Area Under the Curve (ROC-AUC) of 0.89, an accuracy of 0.72, a sensitivity of 0.97, and a specificity of 0.68, while the latter achieved a ROC-AUC of 0.86, an accuracy of 0.71, sensitivity of 0.94 and specificity of 0.67 respectively. Conclusions: Our predictive mortality model may offer providers a means for optimizing the utilization of resources when managing a large caseload, especially with shift changes.
Control of a Flexible Manipulator With Artificial Muscle-Type Pneumatic Actuators, Using μ-Synthesis

In this work, position and vibration control of a flexible one-link manipulator, with an unknown but bounded payload mass and a pair of artificial muscle-type pneumatic actuators, are investigated both analytically and experimentally. A robot with flexible links originally drew attention for its capability to generate fast motion with small-powered actuators. A flexible-link robot also has advantages over a rigid-link robot in the sense that it is much safer when it comes into contact with its environment, including humans. Furthermore, for the sake of safety, it would be more desirable if an actuator could deliver required force while maintaining proper compliance. An artificial muscle-type pneumatic actuator is adequate for such cases. However, it is difficult to make an effective control scheme for this type of robot due to the nonlinearity and uncertainties on the dynamics of the actuator and the vibration of the flexible link. In this study, a controller based on μ-synthesis is developed. Robust performances on the accurate positioning of the arm and vibration suppression of the flexible link are achieved against various model uncertainties on these actuators, the flexible link, the payload, and sensor noise. The effectiveness of the proposed control scheme is confirmed through simulations and experiments.
Effect of Blend Composition on Barrier Properties of Insulating Mats Produced from Local Wool and Waste Bast Fibres

This paper concerns the management of natural waste fibres. The aim of this research was the production of multifunctional acoustic and thermal insulation materials from natural protein and lignocellulosic fibre wastes, according to a circular bioeconomy. For the manufacture of the materials, local mountain sheep wool and a mixture of bast fibre waste generated by string production were used. Insulating materials in the form of mats produced by the needle-punching technique with different fibre contents were obtained. The basic parameters of the mats, i.e., the thickness, surface weight and air permeability were determined. To assess barrier properties, sound absorption and noise reduction coefficients, as well as thermal resistance and thermal conductivity, were measured. It was shown that the mats exhibit barrier properties in terms of thermal and acoustic insulation related to the composition of the mat. It was found that mats with a higher content of the bast fibres possess a greater ability to absorb sounds, while mats with higher wool contents exhibit better thermal insulation properties. The produced mats can serve as a good alternative to commonly used acoustic and thermal insulating materials. The production of the described materials allows for a reduction in the amount of natural fibre waste and achieves the goal of “zero waste” according to the European Green Deal strategy.
Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics

Pseudomonas aeruginosa is an important Gram-negative opportunistic pathogen which causes many severe acute and chronic infections with high morbidity, and mortality rates as high as 40%. What makes P. aeruginosa a particularly challenging pathogen is its high intrinsic and acquired resistance to many of the available antibiotics. In this review, we review the important acute and chronic infections caused by this pathogen. We next discuss various animal models which have been developed to evaluate P. aeruginosa pathogenesis and assess therapeutics against this pathogen. Next, we review current treatments (antibiotics and vaccines) and provide an overview of their efficacies and their limitations. Finally, we highlight exciting literature on novel antibiotic-free strategies to control P. aeruginosa infections.
The Diagnostic Approach towards Combined Hepatocellular-Cholangiocarcinoma—State of the Art and Future Perspectives

Simple Summary Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a specific form of primary liver cancer with features of both hepatocellular and biliary tract cancer. This review provides an overview about the current state-of-the-art diagnostic workup in patients with cHCC-CCA and discusses future perspectives. Differentiating cHCC-CCA from other liver tumours is crucial for the optimal treatment decision. The diagnostic workup to date mainly consists of the evaluation of the clinical features, laboratory tests, radiological imaging and histopathological evaluation of biopsies. During that process, several potential difficulties arise, which we discuss in this review. Abstract Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer which displays clinicopathologic features of both hepatocellular (HCC) and cholangiocellular carcinoma (CCA). The similarity to HCC and CCA makes the diagnostic workup particularly challenging. Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are blood tumour markers related with HCC and CCA, respectively. They can be used as diagnostic markers in cHCC-CCA as well, albeit with low sensitivity. The imaging features of cHCC-CCA overlap with those of HCC and CCA, dependent on the predominant histopathological component. Using the Liver Imaging and Reporting Data System (LI-RADS), as many as half of cHCC-CCAs may be falsely categorised as HCC. This is especially relevant since the diagnosis of HCC may be made without histopathological confirmation in certain cases. Thus, in instances of diagnostic uncertainty (e.g., simultaneous radiological HCC and CCA features, elevation of CA 19-9 and AFP, HCC imaging features and elevated CA 19-9, and vice versa) multiple image-guided core needle biopsies should be performed and analysed by an experienced pathologist. Recent advances in the molecular characterisation of cHCC-CCA, innovative diagnostic approaches (e.g., liquid biopsies) and methods to analyse multiple data points (e.g., clinical, radiological, laboratory, molecular, histopathological features) in an all-encompassing way (e.g., by using artificial intelligence) might help to address some of the existing diagnostic challenges.