Miracle-dz/UniFAR-FTUs huggingface dataset:
Autolysosomal activation combined with lysosomal destabilization efficiently targets myeloid leukemia cells for cell death

Introduction Current cancer research has led to a renewed interest in exploring lysosomal membrane permeabilization and lysosomal cell death as a targeted therapeutic approach for cancer treatment. Evidence suggests that differences in lysosomal biogenesis between cancer and normal cells might open a therapeutic window. Lysosomal membrane stability may be affected by the so-called ‘busy lysosomal behaviour’ characterized by higher lysosomal abundance and activity and more intensive fusion or interaction with other vacuole compartments. Methods We used a panel of multiple myeloid leukemia (ML) cell lines as well as leukemic patient samples and updated methodology to study auto-lysosomal compartment, lysosomal membrane permeabilization and lysosomal cell death. Results Our analyses demonstrated several-fold higher constitutive autolysosomal activity in ML cells as compared to human CD34+ hematopoietic cells. Importantly, we identified mefloquine as a selective activator of ML cells' lysosomal biogenesis, which induced a sizeable increase in ML lysosomal mass, acidity as well as cathepsin B and L activity. Concomitant mTOR inhibition synergistically increased lysosomal activity and autolysosomal fusion and simultaneously decreased the levels of key lysosomal stabilizing proteins, such as LAMP-1 and 2. Discussion In conclusion, mefloquine treatment combined with mTOR inhibition synergistically induced targeted ML cell death without additional toxicity. Taken together, these data provide a molecular mechanism and thus a rationale for a therapeutic approach for specific targeting of ML lysosomes.
Iron-tracking strategies: Chaperones capture iron in the cytosolic labile iron pool

Cells express hundreds of iron-dependent enzymes that rely on the iron cofactors heme, iron-sulfur clusters, and mono-or di-nuclear iron centers for activity. Cells require systems for both the assembly and the distribution of iron cofactors to their cognate enzymes. Proteins involved in the binding and trafficking of iron ions in the cytosol, called cytosolic iron chaperones, have been identified and characterized in mammalian cells. The first identified iron chaperone, poly C-binding protein 1 (PCBP1), has also been studied in mice using genetic models of conditional deletion in tissues specialized for iron handling. Studies of iron trafficking in mouse tissues have necessitated the development of new approaches, which have revealed new roles for PCBP1 in the management of cytosolic iron. These approaches can be applied to investigate use of other nutrient metals in mammals.
Personalized surgical planning for coronary bypass graft configurations using patient-specific computational modeling to avoid flow competition in arterial grafts

Objectives Flow competition between coronary artery bypass grafts (CABG) and native coronary arteries is a significant problem affecting arterial graft patency. The objectives of this study were to compare the predictive hemodynamic flow resulting from various total arterial grafting configurations and to evaluate whether the use of computational fluid dynamics (CFD) models capable of predicting flow can assist surgeons to make better decisions for individual patients by avoiding poorly functioning grafts. Methods Sixteen cardiac surgeons declared their preferred CABG configuration using bilateral internal mammary and radial arteries for each of 5 patients who had differing degrees of severe triple vessel coronary disease. Surgeons selected both a preferred 'aortic' strategy, with at least one graft arising from the ascending aorta, and a preferred “anaortic” strategy which could be performed as a “no-aortic touch” operation. CT coronary angiograms of the 5 patients were coupled to CFD models using a novel flow solver “COMCAB. ” Twelve different CABG configurations were compared for each patient of which 4 were “aortic” and 8 were “anaortic. ” Surgeons then selected their preferred grafting configurations after being shown predictive hemodynamic metrics including functional assessment of stenoses (instantaneous wave-free ratio; fractional flow reserve), transit time flowmetry graft parameters (mean graft flow; pulsatility index) and myocardial perfusion. Results A total of 87.5% (7/8) of “anaortic” configurations compared to 25% (1/4) of “aortic” configurations led to unsatisfactory grafts in at least 1 of the 5 patients (P = 0.038). The use of the computational models led to a significant decrease in the selection of unsatisfactory grafting configurations when surgeons employed “anaortic” (21.25% (17/80) vs. 1.25% (1/80), P < 0.001) but not “aortic” techniques (5% (4/80) vs. 0% (0/80), P = 0.64). Similarly, there was an increase in the selection of ideal configurations for “anaortic” (6.25% (5/80) vs. 28.75% (23/80), P < 0.001) but not “aortic” techniques (65% (52/80) vs. 61.25% (49/80), P = 0.74). Furthermore, surgeons who planned to use more than one unique “anaortic” configuration across all 5 patients increased (12.5% (2/16) vs. 87.5% (14/16), P<0.001). Conclusions “COMCAB” is a promising tool to improve personalized surgical planning particularly for CABG configurations involving composite or sequential grafts which are used more frequently in anaortic operations.
The value of motherhood and psychological distress among infertile women: The mediating role of coping strategies

Introduction The present study investigated psychological distress and coping strategies among infertile women during the COVID-19 pandemic using a multi-dimensional model of infertility-related stress. We explored the associations between individual (i.e., age) and situational characteristics related to infertility (i.e., duration of infertility, cause of infertility, number of lost pregnancies, and assisted reproductive techniques [ART] status), and perceived-infertility-related factors (i.e., the perceived importance of motherhood). Methods Our total sample consisted of 193 women aged 20 to 46 (M= 33.23, SD = 4.58), out of which 102 were undergoing ART procedures (M = 33.60, SD = 4.23), and 91 were not (M= 32.81, SD = 4.94). Participants filled in questionnaires measuring psychological distress, coping strategies, and the importance of motherhood. Results Correlation analyses suggested that the importance of motherhood was positively associated with psychological distress and negative coping strategies. Mediation analysis results indicated that both in the overall sample and in the sample of women undergoing ART procedures, the negative self-perception fully mediated the link between the importance of motherhood on psychological distress. In the non-ART sample, we found a significant mediation effect of denial on the link between the importance of motherhood and psychological distress. Discussion We discuss the theoretical and practical implications of the present findings, focusing on the mental health-related consequences of the social stigma of infertility heightened by the pressure of parenthood.
The nematode Caenorhabditis elegans and diverse potential invertebrate vectors predominantly interact opportunistically

Some small animals migrate with the help of other, more mobile animals (phoresy) to leave short-lived and resource-poor habitats. The nematode Caenorhabditis elegans lives in ephemeral habitats such as compost, but has also been found associated with various potential invertebrate vectors. Little research has been done to determine if C. elegans is directly attracted to these invertebrates. To determine whether C. elegans is attracted to compounds and volatile odorants of invertebrates, we conducted chemotaxis experiments with the isopods Porcellio scaber, Oniscus asellus, and Armadillidium sp. and with Lithobius sp. myriapods, Drosophila melanogaster fruit flies, and Arion sp. slugs as representatives of natural vectors. Because phoresy is an important escape strategy in nature, especially for dauer larvae of C. elegans, we examined the attraction of the natural C. elegans isolate MY2079 in addition to the laboratory-adapted strain N2 at the dauer and L4 stage. We found that DMSO washing solution of Lithobius sp. and the odor of live D. melanogaster attracted C. elegans N2 L4 larvae. Surprisingly, the natural isolate MY2079 was not attracted to any invertebrate during either the dauer or L4 life stages and both C. elegans strains were repelled by various compounds from O. asellus, P. scaber, Armadillidium sp. , Lithobius sp. , and Arion sp. feces. We hypothesize that this is due to defense chemicals released by the invertebrates. Although compounds from Lithobius sp. and D. melanogaster odorants were mildly attractive, the lack of attraction to most invertebrates suggests a predominantly opportunistic association between C. elegans and invertebrate vectors.
General anesthesia vs. non-general anesthesia for vertebrobasilar stroke endovascular therapy

Background The optimal type of anesthesia for acute vertebrobasilar artery occlusion (VBAO) remains controversial. We aimed to assess the influence of anesthetic management on the outcomes in VBAO patients received endovascular treatment (EVT). Methods Patients underwent EVT for acute VBAO at 21 stroke centers in China were retrospectively enrolled and compared between the general anesthesia (GA) group and non-GA group. The primary outcome was the favorable outcome, defined as a modified Rankin Scale (mRS) score 0–3 at 90 days. Secondary outcomes included functional independence (90-day mRS score 0–2), and the rate of successful reperfusion. The safety outcomes included all-cause mortality at 90 days, the occurrence of any procedural complication, and the rate of symptomatic intracranial hemorrhage (sICH). In addition, we performed analyses of the outcomes in subgroups that were defined by Glasgow Coma Scale (GCS) score (≤8 or >8). Results In the propensity score matched cohort, there were no difference in the primary outcome, secondary outcomes and safety outcomes between the two groups. Among patients with a GCS score of 8 or less, the proportion of successful reperfusion was significantly higher in the GA group than the non-GA group (aOR, 3.57, 95% CI 1.06–12.50, p = 0.04). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar results were found. Conclusions Patients placed under GA during EVT for VBAO appear to be as effective and safe as non-GA. Furthermore, GA might yield better successful reperfusion for worse presenting GCS score (≤8). Registration URL: http://www.chictr. org.cn/; Unique identifier: ChiCTR2000033211.
Noise-modulated multistable synapses in a Wilson-Cowan-based model of plasticity

Frequency-dependent plasticity refers to changes in synaptic strength in response to different stimulation frequencies. Resonance is a factor known to be of importance in such frequency dependence, however, the role of neural noise in the process remains elusive. Considering the brain is an inherently noisy system, understanding its effects may prove beneficial in shaping therapeutic interventions based on non-invasive brain stimulation protocols. The Wilson-Cowan (WC) model is a well-established model to describe the average dynamics of neural populations and has been shown to exhibit bistability in the presence of noise. However, the important question of how the different stable regimes in the WC model can affect synaptic plasticity when cortical populations interact has not yet been addressed. Therefore, we investigated plasticity dynamics in a WC-based model of interacting neural populations coupled with activity-dependent synapses in which a periodic stimulation was applied in the presence of noise of controlled intensity. The results indicate that for a narrow range of the noise variance, synaptic strength can be optimized. In particular, there is a regime of noise intensity for which synaptic strength presents a triple-stable state. Regulating noise intensity affects the probability that the system chooses one of the stable states, thereby controlling plasticity. These results suggest that noise is a highly influential factor in determining the outcome of plasticity induced by stimulation.
Far‐infrared generation by doubly resonant difference frequency mixing in a coupled quantum well two‐dimensional electron gas system

Far‐infrared generation (λ=60 μm) by difference‐frequency mixing in a coupled quantum well two‐dimensional electron system is reported. Extremely large values of the nonlinear susceptibility are found (χω2−ω1(2)−10−6 m/V) by engineering a doubly resonant structure with narrow intersubband transition linewidths (Γ∼1–2 meV). The effect of many body interactions (depolarization shift) on the frequency dependence of the process is observed.
Deep learning of bone metastasis in small cell lung cancer: A large sample-based study

Introduction Bone is a common metastatic site for small cell lung cancer (SCLC). Bone metastasis (BM) in patients have are known to show poor prognostic outcomes. We explored the epidemiological characteristics of BM in SCLC patients and create a new deep learning model to predict outcomes for cancer-specific survival (CSS) and overall survival (OS). Materials and Methods Data for SCLC patients diagnosed with or without BM from 2010 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the effects of prognostic variables on OS and CSS. Through integration of these variables, nomograms were created for the prediction of CSS and OS rates at 3-month,6- month,and 12-month. Harrell's coordination index, calibration curves,and time- dependent ROC curves were used to assess the nomograms' accuracy. Decision tree analysis was used to evaluate the clinical application value of the established nomogram. Results In this study, 4201 patients were enrolled. Male sex, tumor size 25 but <10, brain and liver metastases, as well as chemotherapy were associated with a high risk for BM. Tumor size, Age, N stage, gender, liver metastasis, radiotherapy as well as chemotherapy were shown to be prognostic variables for OS, and the prognostic variables for CSS were added to the tumor number in addition. Based on these results, nomograms for CSS and OS were established separately. Internal as well as external validation showed that the C-index, calibration cuurve and DCA had good constructive correction effect and clinical application value. Decision tree analysis further confirmed the prognostic factors of OS and CSS. Discussion The nomogram and decision tree models developed in this study effectively guided treatment decisions for SCLC patients with BM. The creation of prediction models for BM SCLC patients may be facilitated by deep learning models.
Spatial structure and influencing factors of regional city supply networks in manufacturing: A case study of Shandong, China

COVID-19 has driven the formation of regional supply chains. In addition, cities became the basic units of intra-regional supply chain organization under urban administrative economies. Based on the data mining of the buyer-supplier relationship of listed manufacturing firms, this study explores the spatial characteristics of city supply networks within Shandong by the indexes of degree centrality, closeness centrality, betweenness centrality, eigenvector centrality, and a community detection algorithm using the social network analysis (SNA) method and ArcGIS software. It investigates the influencing factors of city supply networks by the correlation and regression of the quadratic assignment procedure (QAP). The results show the following: 1) Shandong has formed a multi-center city supply network with Jinan, Qingdao, Yantai-Weihai, and the distribution pattern of city centrality measured by different centrality indicators shows differences. 2) Cities belonging to the same network community show a coexistence of spatial proximity and “enclave” distribution. 3) Geographic proximity, convenient transportation links, administrative district economy, similarity of business environments represented by development zones, export-oriented or domestic market-oriented division of labor between cities, value chain division of labor between cities, and land price differences between cities promote the formation of regional city supply networks. Conversely, differences in local market size and wage levels between cities hinder the formation of city supply networks. This study attempts to apply the analysis results to regional planning from the perspective of regional industrial synergy development. Additionally, as it is based on typical Chinese provinces, it can provide policy references for national administrative regions and countries/regions at similar spatial scales for manufacturing supply chains, as well as for regional spatial layout decisions of manufacturing enterprises.
Evaluation of global Cenchrus germplasm for key nutritional and silage quality traits

Cenchrus is important genera of grasses inhabiting tropical pastures and the Indian grasslands system. Its forage value is well established to sustain nomadic livestock and wildlife. This study deals with the evaluation of the representative set of global Cenchrus germplasm collection with 79 accessions belonging to six species (C. ciliaris, C. setigerus, C. echinatus, C. myosuroides, C. pennisetiformis, and C. biflorus) at flowering stage. Crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), cellulose, and lignin values were in the range of 61.1–136, 640–749, 373–490, 277–375, and 35.6–75.50 g kg−1DM, respectively, while sugar contents varied from 11.6 to 101 mg g−1 DM. From the evaluated germplasm, 14 accessions of C. ciliaris having >70 mg g−1 DM sugar contents were selected and further evaluated for protein, fiber, carbohydrate and protein fractions, palatability indices, in vitro CH4 production, and ensiling traits. Protein contents were lower in EC397323 (61.8) and higher in IG96-96 (91.5), while the NDF, ADF, cellulose, and lignin contents varied between 678–783, 446–528, 331–405, and 39.6–62.0 g kg−1DM, respectively. The carbohydrate and protein fractions of selected accessions differed (p < 0.05), and the sugar contents varied (p < 0.05) between 74.6 and 89.6 mg−1g DM. Dry matter intake (DMI) and relative feed value (RFV) of accessions varied (p < 0.05) and were in the range of 1.53–1.77% and 58.2–73.8 g kg−1 DM, respectively. The total digestible nutrients (TDNs), digestible energy (DE), and metabolizable energy (ME) of selected accessions varied between 362–487 g kg−1 DM, 6.62–8.90, and 5.42–7.29 Mj kg−1 DM, respectively. In vitro gas and CH4 production (24 h) varied (p < 0.05) between 73.1 to 146 and 7.72 to 21.5 ml/g, respectively, while the degraded dry matter (g kg−1 DM) and CH4 (ml/g DDM) ranged between 399–579 and 17.4–47.2, respectively. The DM contents at ensiling, silage pH, and lactic acid contents of accessions differed (p < 0.05) and ranged between 185–345 g kg−1 DM, 5.10–6.05, and 1.39–23.3 g kg−1 DM, respectively. Wide genetic diversity existed in germplasm and selected C. ciliaris accessions for protein fiber, energy, sugar, and other nutritional traits. Silage prepared from EC397366, IG96-96, IG96-50, and EC397323 had pH and lactic acid contents acceptable for moderate to good quality silage of tropical range grasses.
Genetic diversity of Contracaecum rudolphii sp. A (Nematoda: Anisakidae) parasitizing the European Shag Phalacrocorax aristotelis desmarestii from the Spanish Mediterranean coast

Sibling species of the Contracaecum rudolphii (s.l.) complex are habitual endoparasites of cormorants of the Phalacrocoracidae family, worldwide. In Europe, the two species, C. rudolphii sp. A and C. rudolphii sp. B, have been identified. However, information regarding the occurrence and distribution of these anisakids in cormorants from Spain is scarce. In the present study, 20 specimens of the European Shag, Ph. aristotelis desmarestii, from the western Mediterranean Spanish marine coast were parasitologically analyzed for the presence of nematodes. All hosts were found parasitized with Contracaecum specimens (n = 1,517). A representative subsample was genetically identified as C. rudolphii sp. A by sequence analysis of the mtDNA cox2 gene and the ITS1 and ITS2 regions of the rDNA. This represents the first report of C. rudolphii sp. A from the Spanish Mediterranean waters. Population genetic analysis was performed including other C. rudolphii sp. A specimens from the west Sardinian and the Tyrrhenian Sea. At the intraspecific level, a significant genetic differentiation (Fst ≈ 0.08, p < 0.00001) between the metapopulation from the Spanish Mediterranean coast and that from the Sardinian waters was observed; whereas, no differentiation was found between metapopulations of the parasite from the Spanish and the Tyrrhenian Italian coast. The findings highly support the hypothesis of the adaptation of the life cycle of C. rudolphii sp. A in brackish and marine ecosystems. Furthermore, the results on the population genetics of C. rudolphii sp. A suggest the possible role of the migration routes of wintering populations of cormorants in the Mediterranean Sea in influencing the parasite genetic structure.
Distribution-induced non-universality of the percolation conductivity exponents

The power law which characterises the behaviour of the conductivity of an inhomogeneous conductor near the percolation threshold should generally be independent of the distribution from which the conducting elements are chosen. Some counterexamples, in which a sufficiently anomalous distribution can alter the conduction threshold exponents, are exhibited. Specifically, it is claimed that a network randomly composed of insulating bonds ( sigma =0) and bonds chosen from a distribution behaving as sigma - alpha for small sigma will give the usual exponent t for alpha 2, but in the case 1< beta <or=2 the excess of large conductances alters the exponent to S=s+(2- beta )/( beta -1).
Classification of multispectral images by using Lagrangian support vector machines

Lagragian support vector machine (LSVM) is a linearly convergent Lagrangian, which is obtained by reformulating the quadratic program of a standard linear support vector machine. To investigate the performance of the classifier working on multispectral images with LSVM as optimizer, we devise a new test based on LSVMs for classifying multispectral data in this work. First of all, data are preprocessed. To acquire the optimum bands for image classification, multispectral image is mapped into a two-dimensional feature space to inspect the bands with redundant spectral information. These extracted data acquired through the feature selection is named data group B relative to the original data group A for a purpose of comparison. Then, to classify multiclass problem, binary classification is extended to multiclass classification by pairwise method. Secondly, two groups of data are trained to find models. In this phase, optimal C values are chosen carefully through trials with different values. Then, classifiers based on LSVMs with optimal C values are used to yield optimal separating hyperplane (OSH). Lastly, in prediction phase, the two groups of data are inputted respectively into each classifier for testing. These classifiers include ones with linear kernel and ones with polynomial kernel of degree 2. The results of the experiment reveal that classifiers with LSVMs as an optimizer have excellent performances with both linear kernel and polynomial kernel of degree 2. Bias caused by the differentia of the two groups of data is not obvious.