Miracle-dz/UniFAR-FTUs huggingface dataset:
Early detection of metabolic dysregulation using water T2 analysis of biobanked samples

Background The ability to use frozen biobanked samples from cohort studies and clinical trials is critically important for biomarker discovery and validation. Here we investigated whether plasma and serum water transverse relaxation times (T2) from frozen biobanked samples could be used as biomarkers for metabolic syndrome (MetS) and its underlying conditions, specifically insulin resistance, dyslipidemia, and subclinical inflammation. Methods Plasma and serum aliquots from 44 asymptomatic, non-diabetic human subjects were biobanked at –80°C for 7–9 months. Water T2 measurements were recorded at 37°C on 50 µL of unmodified plasma or serum using benchtop nuclear magnetic resonance relaxometry. The T2 values for freshly drawn and once-frozen-thawed (“frozen”) samples were compared using Huber M-values (M), Lin concordance correlation coefficients (ρc), and Bland–Altman plots. Water T2 values from frozen plasma and serum samples were compared with >130 metabolic biomarkers and analyzed using multi-variable linear/logistic regression and ROC curves. Results Frozen plasma water T2 values were highly correlated with fresh (M=0.94, 95% CI 0.89, 0.97) but showed a lower level of agreement (ρc=0.74, 95% CI 0.62, 0.82) because of an average offset of −5.6% (−7.1% for serum). Despite the offset, frozen plasma water T2 was strongly correlated with markers of hyperinsulinemia, dyslipidemia, and inflammation and detected these conditions with 89% sensitivity and 91% specificity (100%/63% for serum). Using optimized cut points, frozen plasma and serum water T2 detected hyperinsulinemia, dyslipidemia, and inflammation in 23 of 44 subjects, including nine with an early stage of metabolic dysregulation that did not meet the clinical thresholds for prediabetes or MetS. Conclusion Plasma and serum water T2 values from once-frozen-thawed biobanked samples detect metabolic dysregulation with high sensitivity and specificity. However, the cut points for frozen biobanked samples must be calibrated independent of those for freshly drawn plasma and serum.
The Toxicity of Silver Nanoparticles (AgNPs) to Three Freshwater Invertebrates With Different Life Strategies: Hydra vulgaris, Daphnia carinata, and Paratya australiensis

The toxicity of manufactured nanoparticles varies greatly depending on the test species in consideration and estimates of toxicity may also be confounded by test media in which the organisms are cultured. For a more comprehensive toxicity evaluation, species at different trophic levels or with life strategies, tested in different media should be included. In this study, we examined the toxicity of tyrosine-coated silver nanonparticles (tyr-AgNP) to three Australian freshwater invertebrates: Hydra vulgaris, Daphnia carinata and Paratya australiensis. Tyr-AgNPs were synthesized, characterized and their behaviour was examined in different media used for acute toxicity tests. Additionally, the sensitivity of tested organisms to tyr-AgNPs was compared to ionic silver (Ag+). Based on the LC50 values of both tyr-AgNPs and Ag+ ions at different time points, D. carinata was found to be the most sensitive species followed by P. australiensis and H. vulgaris. NP stability studies revealed that tyr-AgNPs were least stable in hydra medium followed by daphnid and shrimp media. This study demonstrates that significant differences in NP toxicity to aquatic organisms exist and the test media and the life strategy of the species play a key role in these differences. Therefore, it is recommended that a multispecies approach is used in predictive risk assessment of NPs and to ensure protection of native species from possible toxic effects from NPs released into aquatic systems. Also recommended is to carefully investigate the fate and behaviour of NPs in different media in assessing NP toxicity and emphasize the need to use native species in developing relevant regulatory frameworks.
Psychological stress effects on myelin degradation in the cuprizone‐induced model of demyelination

Multiple sclerosis (MS) is known as the most common demyelinating disease worldwide in which previous studies have shown that stress is a risk factor for the disease's onset and progression. Nevertheless, further studies are needed to investigate the consequences of stress in MS pathology. In this study, after 5 days of exposure to psychological and physical stress as a repetitive distress modality, rats were treated with cuprizone. The demyelination degree was compared in animal groups using Luxol fast blue staining, immunohistochemical staining for myelin basic protein and transmission electron microscopy. Outcomes revealed that animals exposed to stress prior to cuprizone ingestion, elicit more intense demyelination. Continuous psychological distress has more severe effects on myelin sheath destruction in the preclinical stage.
An Active-Passive Measurement Study of TCP Performance over LTE on High-speed Rails

High-speed rail (HSR) systems potentially provide a more efficient way of door-to-door transportation than airplane. However, they also pose unprecedented challenges in delivering seamless Internet service for on-board passengers. In this paper, we conduct a large-scale active-passive measurement study of TCP performance over LTE on HSR. Our measurement targets the HSR routes in China operating at above 300 km/h. We performed extensive data collection through both controlled setting and passive monitoring, obtaining 1732.9 GB data collected over 135719 km of trips. Leveraging such a unique dataset, we measure important performance metrics such as TCP goodput, latency, loss rate, as well as key characteristics of TCP flows, application breakdown, and users' behaviors. We further quantitatively study the impact of frequent cellular handover on HSR networking performance, and conduct in-depth examination of the performance of two widely deployed transport-layer protocols: TCP CUBIC and TCP BBR. Our findings reveal the performance of today's commercial HSR networks "in the wild'', as well as identify several performance inefficiencies, which motivate us to design a simple yet effective congestion control algorithm based on BBR to further boost the throughput by up to 36.5%. They together highlight the need to develop dedicated protocol mechanisms that are friendly to extreme mobility.
Time‐resolved interaction proteomics of the GIGANTEA protein under diurnal cycles in Arabidopsis

The plant‐specific protein GIGANTEA (GI) controls many developmental and physiological processes, mediating rhythmic post‐translational regulation. GI physically binds several proteins implicated in the circadian clock, photoperiodic flowering, and abiotic stress responses. To understand GI's multifaceted function, we aimed to comprehensively and quantitatively identify potential interactors of GI in a time‐specific manner, using proteomics on Arabidopsis plants expressing epitope‐tagged GI. We detected previously identified (in)direct interactors of GI, as well as proteins implicated in protein folding, or degradation, and a previously uncharacterized transcription factor, CYCLING DOF FACTOR6 (CDF6). We verified CDF6's direct interaction with GI, and ZEITLUPE/FLAVIN‐BINDING, KELCH REPEAT, F‐BOX 1/LIGHT KELCH PROTEIN 2 proteins, and demonstrated its involvement in photoperiodic flowering. Extending interaction proteomics to time series provides a data resource of candidate protein targets for GI's post‐translational control.
PSİKOLOJİK SÖZLEŞME İHLALİNİN YENİLİKÇİ DAVRANIŞA ETKİSİ: ÖRGÜTSEL SESSİZLİĞİN ROLÜ: SAVUNMA SANYİİNDE BİR UYGULAMA

Yenilikci davranis, isyerinde urun ve uygulamalara iliskin yeni fikirlerin uretilmesi olarak tanimlanabilir. Psikolojik sozlesme ise calisan davranislarinin onemli bir belirleyicisidir. Psikolojik sozlesmenin ihlaline yonelik bir algi, calisanlarda olumsuz tutum ve davranislara neden olabilmektedir. Calisanlarin psikolojik sozlesmelerinin ihlal edildigine yonelik algilari, psikolojik ve guvenlige iliskin endiselerinden dolayi sessiz kalmalarina neden olmaktadir. Bu calismanin amaci, psikolojik sozlesme ihlalinin yenilikci davranisa etkisi ve bu iliskide orgutsel sessizligin aracilik rolunu incelemektir. Arastirma verileri, savunma sanayiinde faaliyet gosteren iki farkli firmada calisan toplam 213 kisiden elde edilmistir. Olceklerin yapi gecerliligi dogrulayici faktor analiziyle; degiskenler arasindaki iliskiler ve aracilik etkisi korelasyon ve regresyon analiziyle incelenmistir. Analiz sonuclari psikolojik sozlesme ihlalinin calisanlarin yenilikci davranisini olumsuz olarak etkiledigini ve orgutsel sessizligin bu iliskide tam aracilik etkisine sahip oldugunu gostermektedir. Arastirma bulgularinin uygulamalari ve gelecekte yapilabilecek calismalar icin oneriler tartisilmistir.
Mycobacterium “habana” TMC 5135 as a vaccine candidate against tuberculosis: In vitro studies

Background: Tuberculosis (TB) is one of the biggest problems of global health, at present. Bacillus–Calmette–Guérin is the only vaccine available against this disease. It protects only against the severe forms of TB in the childhood, which is a challenge in the search of new vaccine candidates. Taking into account the protective history of Mycobacterium “habana” against experimental TB, we proposed to provide the elements that support the use of M. “habana” TMC 5135 as a vaccine candidate against TB by infection studies in murine macrophages cell cultures. Methods: The production of microbicidal compounds dependent on oxygen metabolism as nitric oxide and hydrogen peroxide by murine peritoneal macrophages was detected. The invasive and toxigenic capacity of M. “habana” to infect this cell type was also evaluated through the quantification of intracellular alive bacillus and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, respectively. Results: The results suggest that M. “habana” TMC 5135 is able to persist into peritoneal macrophages, to resist the effectors mechanisms of respiratory burst, and to keep the viability of the target cell. The demonstration of these effector mechanisms and the survival capacity of M. “habana” in this niche are relevant aspects of this research assuring the continuity of this candidate to next phases of preclinical development. Conclusion: The present investigation contributes to the characterization of the infection by this mycobacteria in its main target cells of innate immunity and it suggest future investigations to evaluate the activation of effector mechanisms of the innate immunity against this candidate.
TraPHic: Trajectory Prediction in Dense and Heterogeneous Traffic Using Weighted Interactions

We present a new algorithm for predicting the near-term trajectories of road agents in dense traffic videos. Our approach is designed for heterogeneous traffic, where the road agents may correspond to buses, cars, scooters, bi-cycles, or pedestrians. We model the interactions between different road agents using a novel LSTM-CNN hybrid network for trajectory prediction. In particular, we take into account heterogeneous interactions that implicitly account for the varying shapes, dynamics, and behaviors of different road agents. In addition, we model horizon-based interactions which are used to implicitly model the driving behavior of each road agent. We evaluate the performance of our prediction algorithm, TraPHic, on the standard datasets and also introduce a new dense, heterogeneous traffic dataset corresponding to urban Asian videos and agent trajectories. We outperform state-of-the-art methods on dense traffic datasets by 30%.
Social stress increases plasma cortisol and reduces forebrain cell proliferation in subordinate male zebrafish (Danio rerio)

ABSTRACT Many animals, including zebrafish (Danio rerio), form social hierarchies through competition for limited resources. Socially subordinate fish may experience chronic stress, leading to prolonged elevation of the glucocorticoid stress hormone cortisol. As elevated cortisol levels can impair neurogenesis, the present study tested the hypothesis that social stress suppresses cell proliferation in the telencephalon of subordinate zebrafish via a cortisol-mediated mechanism. Cell proliferation was assessed using incorporation of the thymidine analogue 5-bromo-2′-deoxyuridine (BrdU). After 48 and 96 h of social interaction, subordinate male zebrafish exhibited elevated plasma cortisol concentrations and significantly lower numbers of BrdU+ cells in the dorsal but not ventral regions of the telencephalon compared with dominant or group-housed control male fish. After a 2 week recovery in a familiar group of conspecifics, the number of BrdU+ cells that co-labelled with a neuronal marker (NeuN) was modestly reduced in previously subordinate male fish, suggesting that the reduction of cell proliferation during social stress may result in fewer cells recruited into the neuronal population. In contrast to male social hierarchies, subordinate female zebrafish did not experience elevated plasma cortisol, and the number of BrdU+ cells in the dorsal telencephalic area was comparable among dominant, subordinate and group-housed control female fish. Treating male zebrafish with metyrapone, a cortisol synthesis inhibitor, blocked the cortisol response to social subordination and attenuated the suppression of brain cell proliferation in the dorsal telencephalic area of subordinate fish. Collectively, these data support a role for cortisol in regulating adult neurogenesis in the telencephalon of male zebrafish during social stress. Summary: Elevated cortisol reduces cell proliferation in the telencephalon of socially subordinate male, but not female, zebrafish.
Integrated analysis reveals key genes with prognostic value in lung adenocarcinoma

Background Lung cancer is one of the most common malignant tumors. Despite advances in lung cancer therapies, prognosis of non-small-cell lung cancer is still unfavorable. The aim of this study was to identify the prognostic value of key genes in lung tumorigenesis. Methods Differentially expressed genes (DEGs) were screened out by GEO2R from three Gene Expression Omnibus cohorts. Common DEGs were selected for Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology enrichment analysis. Protein– protein interaction networks were constructed by the STRING database and visualized by Cytoscape software. Hub genes, filtered from the CytoHubba, were validated using the Gene Expression Profiling Interactive Analysis database, and their genomic alterations were identified by performing the cBioportal. Finally, overall survival analysis of hub genes was performed using Kaplan–Meier Plotter. Results From three datasets, 169 DEGs (70 upregulated and 99 downregulated) were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that upregulated DEGs were significantly enriched in cell cycle, p53 pathway, and extracellular matrix–receptor interactions; the downregulated DEGs were significantly enriched in PPAR pathway and tyrosine metabolism. The protein–protein interaction network consisted of 71 nodes and 305 edges, including 49 upregulated and 22 downregulated genes. The hub genes, including AURKB, BUB1B, KIF2C, HMMR, CENPF, and CENPU, were overexpressed compared with the normal group by Gene Expression Profiling Interactive Analysis analysis, and associated with reduced overall survival in lung cancer patients. In the genomic alterations analysis, two hotspot mutations (S2021C/F and E314K/V) were identified in Pfam protein domains. Conclusion DEGs, including AURKB, BUB1B, KIF2C, HMMR, CENPF, and CENPU, might be potential biomarkers for the prognosis and treatment of lung adenocarcinoma.
Ten genes associated with MGMT promoter methylation predict the prognosis of patients with glioma

Glioma originates from the glial cells of the spine or brain, and promoter methylation of O6-methylguanine-DNA methyltransferase (MGMT) can promote the chemosensitivity of glioma. The present study aimed to reveal the key genes implicated in MGMT promoter methylation in patients with glioma. RNA-sequencing data and methylation data for glioma were extracted from The Cancer Genome Atlas database. Following expression characteristic analysis and differential expression analysis using unsupervised hierarchical clustering and a rank sum test, the feature genes were identified between high and low methylation groups. Furthermore, multivariate survival analysis for the feature genes was performed using the survival package in R. Additionally, the independent glioma RNA expression datasets GSE7696 and GSE42669 were used to validate the prognostic efficiency of the gene combination. The results indicated that the prognosis of the low methylation group was significantly worse than that of the high methylation group. The ten genes corresponding to the cut-off value of 0.56 (Rho GTPase-activating protein 21, CECR2, histone acetyl-lysine reader, endosulfine α, G-patch domain-containing 8, KIAA1109, MGMT, protocadherin β 13, selenoprotein M, sperm-associated antigen 9 and WD repeat domain 6) were able to significantly predict prognosis and were differentially expressed between the two groups. Multivariate survival analysis suggested that the ten genes were effective for sample classification and prognostic prediction. Furthermore, the validation datasets confirmed the correlation of the ten genes with prognosis. In conclusion, these 10 genes may be mediated by MGMT promoter methylation in glioma. In addition, the ten-gene combination may be associated with the prognosis of patients with glioma.
Dosimetric features‐driven machine learning model for DVH prediction in VMAT treatment planning

PURPOSE Few features characterizing the dosimetric properties of the patients are included in currently available dose-volume histogram (DVH) prediction models, making it intractable to build a correlative relationship between the input and output parameters. Here, we use planning target volume (PTV)-only treatment plans of the patients (i.e., the achievable dose distribution in the absence of organs-at-risk (OAR) constraints) to estimate the potentially achievable quality of treatment plans and establish a machine learning-based DVH prediction framework with the use of the dosimetric metric as model input parameters. METHODS A support vector regression (SVR) approach was used as the backbone of our machine learning model. A database containing volumetric modulated arc therapy (VMAT) plans of 63 prostate cancer patients were used. For each patient, the PTV-only plan was generated first. A correlative relationship between the OAR DVH of the PTV-only plan (model input) and the corresponding DVH of the clinical treatment plan (CTP) (model output) was then established with the 53 training cases. The prediction model was tested by the validation cohort of ten cases. RESULTS For the training cohort, the checks of dosimetric endpoints (DEs) indicated that 52 of 53 plans (98%) were within the 10% error bound for bladder, and 45 of 53 plans (85%) were within the 10% error bound for rectum. In the validation tests, 92% and 96% of the DEs were within the 10% error bounds for bladder and rectum, respectively, and eight of ten validation plans (80%) were within the 10% error bound for both the bladder and rectum. The sum of absolute residuals (SAR) achieved a mean of 0.034 ± 0.028 and 0.046 ± 0.021 for the bladder and rectum, respectively. CONCLUSIONS A novel dosimetric features-driven machine learning model with the use of PTV-only plan has been established for DVH prediction. The framework is capable of efficiently generating best achievable DVHs for VMAT planning.
Dominance rank-associated immune gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons

In humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. Experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. However, social hierarchies are established and maintained in different ways across species: while some are based on kin-directed nepotism, others emerge from direct physical competition. We investigated how this variation influences the relationship between social status and immune gene regulation in wild baboons, where hierarchies in males are based on fighting ability but female hierarchies are nepotistic. We measured rank-related variation in gene expression levels in adult baboons of both sexes at baseline and in response to ex vivo stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We identified >2000 rank- associated genes in males, an order of magnitude more than in females. In males, high status predicted increased expression of genes involved in innate immunity and preferential activation of the NFkB-mediated pro-inflammatory pathway, a pattern previously associated with low status in female rhesus macaques. Using Mendelian randomization, we reconcile these observations by demonstrating that high status-associated gene expression patterns are precursors, not consequences, of high social status in males, in support of the idea that physiological condition determines who attains high rank. Together, our work provides the first test of the relationship between social status and immune gene regulation in wild primates. It also emphasizes the importance of social context in shaping the relationship between social status and immune function. SIGNIFICANCE Social status predicts fitness outcomes in social animals, motivating efforts to understand its physiological causes and consequences. We investigated the relationship between social status and immune gene expression in wild baboons, where female status is determined by kinship but male status is determined by fighting ability. We uncover pervasive status-gene expression associations in males, but not females. High status males exhibit high levels of pro-inflammatory gene expression, in contrast to previous findings in hierarchies that are not competitively determined. Using Mendelian randomization, we show that this status-associated variation precedes dominance rank attainment: males who compete successfully for high status are already immunologically distinct. The nature of social hierarchies thus fundamentally shapes the relationship between social status and immune function.