Miracle-dz/UniFAR-FTUs huggingface dataset:
Fetal Superior Vena Cava Blood Flow and Its Fraction of Cardiac Output: A Longitudinal Ultrasound Study in the Second Half of Pregnancy

Introduction: In the fetus, a large proportion of the superior vena cava blood flow (QSVC) comes from the brain. To provide the possibility of using this blood flow as a representation of fetal brain circulation, we aimed to determine the fetal QSVC and its fraction of cardiac output during the second half of physiological pregnancies. Materials and Methods: This was a prospective longitudinal study specifically designed for studying fetal hemodynamic development. Healthy women with singleton low-risk pregnancies were included. Ultrasonography was performed at 4-weekly intervals from 20+0 gestational weeks to term. Doppler velocity recordings of the superior vena cava (SVC) and cardiac ventricular outflow tracts were used to obtain the time-averaged maximum velocities (TAMxV). Vessel diameters were measured to calculate their cross-sectional areas (CSA): π(diameter/2)2. Blood flow (Q) was computed as: h*TAMxV*CSA, h being the spatial blood velocity profile, to obtain QSVC and cardiac outputs. The sum of left and right ventricular cardiac outputs constituted the combined cardiac output (CCO). Ultrasound biometry based estimated fetal weight and brain weight were used to normalize the flow. QSVC was also expressed as the fraction (%) of CCO. Gestational age specific percentiles were established for each blood flow parameter using multilevel modeling. Results: Totally, 134 of the 142 included women were eligible for the study with 575 sets of observations. The SVC mean diameter (19–52 mm), mean TAMxV (8.83–16.14 cm/s), and QSVC (15.4–192.0 ml/min) increased significantly during the second half of pregnancy (p < 0.001) while the mean QSVC normalized by estimated fetal weight (49 ml/min/kg) and by estimated brain weight (50 ml/min/100 g) were relatively stable. Similarly, the mean CCO increased (156–1,776 ml/min; p < 0.001) while the normalized CCO (509 ± 13 ml/min/kg) and QSVC as a fraction of CCO (10 ± 0.92%) did not change significantly with gestational age. Conclusion: We provide reference values for fetal QSVC which increases significantly with gestation, and constitutes roughly 10% of the fetal CCO at any time during the second half of pregnancy.
PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer

The widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of immunotherapy and chemotherapy have shown good clinical expectations. Here, we studied the cooperative effects of chloroquine, an anti-malarial drug that is now widely used in anti-tumor research, and RNA interference (RNAi) targeting the immune checkpoint molecule Programmed Death-1 (PD-1) delivered with attenuated Salmonella. Our results show that chloroquine can not only significantly inhibit the survival of colon cancer cells and induce apoptosis, but also effectively inhibit cell invasion and migration. The results of in vivo experiments show that chloroquine can increase the expression of PD-1 in tumor tissues. Combining chloroquine and PD-1 siRNA can further inhibit the growth and metastases of colon cancer and induce apoptosis. The mechanism underlying this phenomenon is the occurrence of chloroquine-induced apoptosis and the effective immune response caused by the attenuated Salmonella carrying PD-1 siRNA. This study suggests that the combined application of PD-1-based immunotherapy and anti-cancer drugs has become a new expectation for clinical treatment of colorectal cancer.
The Effect of Robotic Assisted Gait Training With Lokomat® on Balance Control After Stroke: Systematic Review and Meta-Analysis

Introduction: Disturbances of balance control are common after stroke, affecting the quality of gait and increasing the risk of falls. Because balance and gait disorders may persist also in the chronic stage, reducing individual independence and participation, they represent primary goals of neurorehabilitation programs. For this purpose, in recent years, numerous technological devices have been developed, among which one of the most widespread is the Lokomat®, an actuated exoskeleton that guide the patient's limbs, simulating a symmetrical bilateral gait. Preliminary evidence suggests that beyond gait parameters, robotic assisted gait training may also improve balance. Therefore, the aim of this systematic review was to summarize evidence about the effectiveness of Lokomat® in improving balance in stroke patients. Methods: Randomized controlled trials published between January 1989 and August 2020, comparing Lokomat® training to conventional therapy for stroke patients, were retrieved from seven electronic databases. Balance, assessed by means of validated clinical scales, was considered as outcome measure. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the methodological quality of the studies. The study protocol was registered on PROSPERO (no. CRD42020197531). Results: After the removal of the duplicates, according to the inclusion criteria, 13 studies were selected, involving 445 subacute or chronic stroke patients. Eleven papers contributed to three meta-analyses. Favorable results for recovery of balance in stroke survivors treated with Lokomat® were shown using Timed Up and Go (pooled mean difference = −3.40, 95% CI −4.35 to −2.44; p < 0.00001) and Rivermead Mobility Index as outcome measures (pooled mean difference = 0.40, 95% CI 0.26–0.55; p < 0.00001). Inconclusive results were found when balance was measured by means of the Berg Balance Scale (pooled mean difference = 0.17, 95% CI −0.26 to 0.60; p = 0.44). Conclusions: Overall, most studies have shown beneficial effects of Lokomat® on balance recovery for stroke survivors, at least comparable to conventional physical therapy. However, due to the limited number of studies and their high heterogeneity, further research is needed to draw more solid and definitive conclusions.
Encouraging Emotional Conversations in Children With Complex Communication Needs: An Observational Case Study

Children with complex communication needs (CCN) regularly have barriers to express and discuss emotions, and have fewer opportunities to participate in emotional conversations. The study explores and analyzes the changes after a training program focused on offering an interactive home learning environment that encouraged and modeled emotion-related conversations between a parent and a child with CCN within storybook-reading contexts. An observational design (nomothetic/follow-up/multidimensional) was used to explore and analyze the changes in the communicative interaction around emotions between mother-child. Augmentative and alternative communication (AAC) technologies were used to provide the child access to emotion-related vocabulary. The training program resulted in the mother providing more opportunities to engage her child in emotional conversations, suggesting that when opportunities and resources to talk about emotions were promoted, the child showed more engagement in emotion-related conversations using his AAC system. The mother–child communicative patterns and behavioral relationships observed during the phases are also presented. This case study illustrates the importance of a primary communication partners’ role in facilitating emotional conversations, and the promising efficacy of a training program implemented in a storybook interactive learning environment to promote conversations about emotion-related events while encouraging children with CCN to learn, explore, express, and discuss emotions.
Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms

DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 (PTBP1) in IA, as well as its potential to predict IA. Forty-eight patients with IA and 48 age- and sex-matched healthy controls were recruited into this study. Methylation levels of CpG sites were determined via bisulfite pyrosequencing. The PTBP1 levels in the blood were determined using a real-time quantitative reverse transcription-polymerase chain reaction test. Significant differences were found between IAs and controls in CpG1 (p = 0.001), CpG2 (p < 0.001), CpG3 (p = 0.037), CpG4 (p = 0.003), CpG5 (p = 0.006), CpG6 (p = 0.02), and mean methylation (p < 0.001). The mRNA level of PTBP1 in the blood was much lower in IAs compared with controls (p = 0.002), and the PTBP1 expression was significantly associated with DNA methylation promoter levels in individuals (r = −0.73, p < 0.0001). In addition, stratification analysis comparing smokers and non-smokers revealed that tobacco smokers had significantly higher levels of DNA methylation in PTBP1 than non-smokers (p = 0.002). However, no statistical difference in PTBP1 methylation was found between ruptured and unruptured IA groups (p > 0.05). The ROC analyses of curves revealed that PTBP1 methylation may be a predictor of IA regardless of sex (both sexes, area under curve (AUC) = 0.78, p < 0.0001; male, AUC = 0.76, p = 0.002; female, AUC = 0.79, p < 0.0001). These findings suggest that long-term tobacco smoke exposure led to DNA methylation in the promoter region of the PTBP1 gene, which further decreased PTBP1 gene expression and participated in the pathogenesis of IA. The methylation of PTBP1 may be a potential predictive marker for the occurrence of IA.
Value of Perampanel as Adjunctive Treatment for Partial-Onset Seizures in Epilepsy: Cost-Effectiveness and Budget Impact Analysis

Introduction: China has ~6 million patients with active epilepsy every year, around 60% of whom suffer from partial-onset seizures. Perampanel (PER) is a novel anti-epileptic drug for partial-onset seizures. PER has been included in the latest Chinese National Reimbursement Drug List (NRDL) in 2020. However, there is still a lack of evaluation evidence on the value of PER in China. Methods: This study selected a health system perspective. A Markov model was established to simulate the lifelong transition of different response levels and calculate the number of seizures in Chinese patients. Based on the utility value and mortality risk, the life years and quality-adjusted life years (QALYs) of patients using PER vs. lacosamide (LCM) were estimated. Efficacy data were derived from clinical trials and the literature. Cost data (in US dollars) included drug costs and medical service costs. A lifetime horizon was adopted. Health outcomes and costs were discounted at an annual discount rate of 5%. Deterministic sensitivity analysis, probability sensitivity analysis, and scenario analysis were performed. The impact of the inclusion of PER in the NRDL on the medical insurance budget over 3 years (2021–2023) was also estimated. Results: Cost-effectiveness analysis indicates that 8 mg/day of PER increases QALYs by 0.054 and saves costs by $2,390 compared with 400 mg/day of LCM. 4 mg/day of PER increases QALYs by 0.010 and saves costs by $860 compared with 200 mg/day of LCM. Deterministic sensitivity analysis reveals that utility value and the extreme discount rate are the factors with the greatest impact on the incremental cost-effectiveness ratio. Probabilistic sensitivity analysis and scenario analysis show that the results are robust. Budget impact analysis indicates that after inclusion of PER in the NRDL, the incremental budget would be $1.28, $2.83, and $4.56 million from 2021 to 2023, respectively, but covering more eligible epileptic patients in the same time (1,918, 4,287, and 8,983, respectively). Conclusion: PER (8 or 4 mg/day) is of relatively high value as an add-on therapeutic regimen for partial-onset seizures in China because of its dominate advantage of cost-effectiveness over LCM and acceptable budget impact.
Waste Is the New Wealth – Recovering Resources From Poultry Wastewater for Multifunctional Microalgae Feedstock

To meet the increasing demands of the growing population and to cope with the challenges of global change, both the production of biological feedstock and the recovery of recyclable natural resources play a critical role. Microalgal biomass is a promising source of renewable multifunctional feedstock, but the production is costly and requires large amounts of water. Here, we explored the potential of using wastewater as culture medium to lower the economic and environmental costs of microalgae biomass production and evaluated its valorization opportunities for animal feed production. As a proof of principle, we show that Chlorella sorokiniana can be cultivated on poultry wastewater, with a 83 and 113% increase in productivity when wastewater was first 50% diluted with tap water or standard growth medium, respectively. Wastewater sterilization before use enhanced algal growth with 36–118%, but only when wastewater was 25–50% diluted with standard medium. In contrast, it offered no additional benefits when dilutions were made with tap water or when wastewater was not diluted. At the end of the 22-days experiment, a maximum biomass of 0.8–1.9 g L−1 was reached for algae grown on wastewater. The produced biomass had a high macronutrient content, and the heavy metal content was below maximum limits for use in animal feed. Likewise, the tested pathogen groups were reduced until below safety norms for feed production after algal growth in unsterilized 50% wastewater (diluted with tap water). Overall, these findings add to our growing knowledge on the cultivation of microalgae on wastewater and its valorization opportunities, paving the way for a more sustainable use and reuse of resources.
New Insight into Post-seismic Landslide Evolution Processes in the Tropics

Earthquakes do not only trigger landslides in co-seismic phases but also elevate post-seismic landslide susceptibility either by causing a strength reduction in hillslope materials or by producing co-seismic landslide deposits, which are prone to further remobilization under the external forces generated by subsequent rainfall events. However, we still have limited observations regarding the post-seismic landslide processes. And, the examined cases are rarely representative of tropical conditions where the precipitation regime is strong and persistent. Therefore, in this study, we introduce three new sets of multi-temporal landslide inventories associated with subsets of the areas affected by 1) 2016 Reuleuet (Indonesia, Mw = 6.5), 2) 2018 Porgera (Papua New Guinea, Mw = 7.5) and 3) 2012 Sulawesi (Indonesia, Mw = 6.3), 2017 Kasiguncu (Indonesia, Mw = 6.6) and 2018 Palu (Indonesia, Mw = 7.5) earthquakes. Overall, our findings show that the landslide susceptibility level associated with the occurrences of new landslides return to pre-seismic conditions in less than a year in the study areas under consideration. We stress that these observations might not be representative of the entire area affected by these earthquakes but the areal boundaries of our study areas.
METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis

Rheumatoid arthritis (RA), a common autoimmune disease, is extremely damaging to human health. Fibroblast-like synoviocytes (FLSs) have a vital role in the occurrence and development of RA. Methyltransferase-like 3 (METTL3), which is a crucial component of the N6-methyladenosine (m6A) methyltransferase complex, is involved in the progression of many diseases. In this study, we explored the role of METTL3 in the inflammatory response and proliferation, invasion, and migration of FLSs. We used human RA synovial tissues and the adjuvant-induced arthritis (AIA) animal model of RA. Experimental results revealed that METTL3 expression was significantly upregulated in human RA synovial tissues and in the rat AIA model. METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs. In contrast, they were increased by METTL3 overexpression. Additionally, we found that, in FLSs, METTL3 may activate the nuclear factor (NF)-κB signaling pathway. The experimental results showed that METTL3 may promote FLS activation and inflammatory response via the NF-κB signaling pathway.
Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.
Organic Acid Exposure Enhances Virulence in Some Listeria monocytogenes Strains Using the Galleria mellonella Infection Model

Prior research has suggested that the use of organic acids in the food industry may unintentionally enhance pathogenicity of Listeria monocytogenes strain N1-227 and R2-499. This study explored the connection between habituation to L-lactic acid or acetic acid and virulence in L. monocytogenes strains N1-227 and R2-499 using selected gene expression analysis and the in vivo Galleria mellonella wax worm model for infection. Expression of transcription factors (sigB and prfA) and genes related to acid resistance (gadD2, gadD3, and arcA) and bile resistance (bsh and bilE) or to virulence (inlA, inlB, hly, plcA, plcB, uhpT, and actA) was investigated by quantitative real-time PCR (qRT-PCR), while in vivo virulence was assessed by following the lethal time to 50% population mortality (LT50) of G. mellonella larvae after injection of untreated and habituated L. monocytogenes. Twenty minutes of habituation to the organic acids at pH 6.0 significantly increased expression of key acid and bile stress response genes in both strains, while expression of virulence genes was strain-dependent. The expression of transcription factor sigB was strain-dependent and there was no significant change in the expression of transcription factor prfA in both strains. Habituation to acid increased virulence of both strains as evidenced by decreased LT50 of G. mellonella larvae injected with Listeria habituated to either acid. In summary, habituation of both L. monocytogenes strains to organic acids up-regulated expression of several stress and virulence genes and concurrently increased virulence as measured using the G. mellonella model.
Inhibition of eIF2α Phosphorylation by Peste des Petits Ruminant Virus Phosphoprotein Facilitates Viral Replication

Peste des petits ruminant virus (PPRV) causes a highly contagious disease in small ruminants. The molecular mechanism of PPRV replication and its interactions with hosts are poorly studied. In other paramyxoviruses, the viral phosphoprotein (P) has been associated with multiple functions for key biological processes such as the regulation of transcription, translation, and the control of cell cycle. Phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) is an important process for gene regulation in host cells under stress, including viral infection. In the present study, molecular mechanisms associated with PPRV replication and viral interaction with host cells were investigated. We describe the ability of PPRV to dephosphorylate eIF2α and the potential of PPRV P protein to induce the host cellular growth arrest DNA damage protein (GADD34), which is known to be associated with eIF2α dephosphorylation. Furthermore, we observed that PPRV P protein alone could block PERK/eIF2α phosphorylation. We speculate that PPRV exploits eIF2α dephosphorylation to facilitate viral replication and that PPRV P protein is involved in this molecular mechanism. This work provides new insights into further understanding PPRV pathobiology and its viral/host interactions.
Response Time Bounds for DAG Tasks with Arbitrary Intra-Task Priority Assignment

Abstract Most parallel real-time applications can be modeled as directed acyclic graph (DAG) tasks. Intra-task priority assignment can reduce the nondeterminism of runtime behavior of DAG tasks, possibly resulting in a smaller worst-case response time. However, intra-task priority assignment incurs dependencies between different parts of the graph, making it a challenging problem to compute the response time bound. Existing work on intra-task task priority assignment for DAG tasks is subject to the constraint that priority assignment must comply with the topological order of the graph, so that the response time bound can be computed in polynomial time. In this paper, we relax this constraint and propose a new method to compute response time bound of DAG tasks with arbitrary priority assignment. With the benefit of our new method, we present a simple but effective priority assignment policy, leading to smaller response time bounds. Comprehensive evaluation with both single-DAG systems and multi-DAG systems demonstrates that our method outperforms the state-of-the-art method with a considerable margin.