Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Associations Between Serum Lipoprotein (a) Levels and Atherosclerotic Vascular Diseases in Hungarian Patients With Familial Hypercholesterolemia Using Data Mining and Machine Learning

Background and aims: Premature mortality due to atherosclerotic vascular disease is very high in Hungary in comparison with international prevalence rates, though the estimated prevalence of familial hypercholesterolemia (FH) is in line with the data of other European countries. Previous studies have shown that high lipoprotein(a)- Lp(a) levels are associated with an increased risk of atherosclerotic vascular diseases in patients with FH. We aimed to assess the associations of serum Lp(a) levels and such vascular diseases in FH using data mining methods and machine learning techniques in the Northern Great Plain region of Hungary. Methods: Medical records of 590,500 patients were included in our study. Based on the data from previously diagnosed FH patients using the Dutch Lipid Clinic Network scores (≥7 was evaluated as probable or definite FH), we trained machine learning models to identify FH patients. Results: We identified 459 patients with FH and 221 of them had data available on Lp(a). Patients with FH had significantly higher Lp(a) levels compared to non-FH subjects [236 (92.5; 698.5) vs. 167 (80.2; 431.5) mg/L, p < . 01]. Also 35.3% of FH patients had Lp(a) levels >500 mg/L. Atherosclerotic complications were significantly more frequent in FH patients compared to patients without FH (46.6 vs. 13.9%). However, contrary to several other previous studies, we could not find significant associations between serum Lp(a) levels and atherosclerotic vascular diseases in the studied Hungarian FH patient group. Conclusion: The extremely high burden of vascular disease is mainly explained by the unhealthy lifestyle of our patients (i.e., high prevalence of smoking, unhealthy diet and physical inactivity resulting in obesity and hypertension). The lack of associations between serum Lp(a) levels and atherosclerotic vascular diseases in Hungarian FH patients may be due to the high prevalence of these risk factors, that mask the deleterious effect of Lp(a).
Construction and Verification of a Combined Hypoxia and Immune Index for Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive malignancies in humans. Hypoxia-related genes are now recognized as a reflection of poor prognosis in cancer patients with cancer. Meanwhile, immune-related genes play an important role in the occurrence and progression of ccRCC. Nevertheless, reliable prognostic indicators based on hypoxia and immune status have not been well established in ccRCC. The aims of this study were to develop a new gene signature model using bioinformatics and open databases and to validate its prognostic value in ccRCC. The data used for the model structure can be accessed from The Cancer Genome Atlas database. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the hypoxia- and immune-related genes associated with prognostic risk, which were used to develop a characteristic model of prognostic risk. Kaplan-Meier and receiver-operating characteristic curve analyses were performed as well as independent prognostic factor analyses and correlation analyses of clinical characteristics in both the training and validation cohorts. In addition, differences in tumor immune cell infiltrates were compared between the high and low risk groups. Overall, 30 hypoxia- and immune-related genes were identified, and five hypoxia- and immune-related genes (EPO, PLAUR, TEK, TGFA, TGFB1) were ultimately selected. Survival analysis showed that the high-risk score on the hypoxia- and immune-related gene signature was significantly associated with adverse survival outcomes. Furthermore, clinical ccRCC samples from our medical center were used to validate the differential expression of the five genes in tumor tissue compared to normal tissue through quantitative real-time polymerase chain reaction (qRT-PCR). However, more clinical trials are needed to confirm these results, and future experimental studies must verify the potential mechanism behind the predictive value of the hypoxia- and immune-related gene signature.
Individual Differences in the Effects of Physical Activity on Classroom Behaviour

Background: Promoting physical activity (PA) in children is associated with a wide range of desired outcomes. With children increasingly not meeting recommended levels of activity, the school setting offers many opportunities to improve this. Increasing children’s on-task behaviour is of particular importance to teachers, and while it has previously been suggested that PA can improve classroom behaviour, a consensus on the dose-response relationship of PA content, and its interaction with children’s individual differences, is yet to be reached. This study aimed to investigate this relationship more closely and assess the differences between objective and subjective measures of PA intensity. Method: Data was collected from 76 primary school-aged children (M age = 9.3 years, SD = 0.7 years; 46 females). The PE lesson intervention followed a 3 (intensity: low, medium, high) by 2 (complexity: low, high) within-person design. Children’s task-behaviour was observed pre- and post-the intervention PE lesson during “business as usual” classroom lesson. PA was measured objectively with wrist-worn accelerometer devices for 24 h before the intervention, and subjectively rated on a five-point Likert scale after each intervention lesson. Results: The results indicated a difference in subjective and objective measures of PA intensity on children’s on-task behaviour. Objective measures positively predicted task-behaviour at moderate to high intensities, whereas subjective ratings were beneficial only at sub-maximal intensity. Findings suggested that boys’ on-task behaviour improved at higher intensities, whereas girls were also responsive to lower intensity lessons. Less active children showed more improvement in on-task behaviour after a range of lessons, whereas more active children only benefited from the highest intensity lessons. Finally, children exhibiting the highest levels of off-task behaviour improved their on-task behaviour after all intervention lessons. Conclusion: The findings suggest that higher intensities of PA have a generally positive effect on children’s subsequent behaviour, although certain individual characteristics make children more responsive to lower PA intensities. Furthermore, passive off-task behaviours were less prevalent after lower-intensity PA. Thus, individual differences, as well as the target behaviour, are important factors to take into account when designing optimal PE lessons for improving classroom behaviour.
Respiratory 4D-Gating F-18 FDG PET/CT Scan for Liver Malignancies: Feasibility in Liver Cancer Patient and Tumor Quantitative Analysis

Purpose To evaluate the potential clinical role and effectiveness of respiratory 4D-gating F-18 FDG PET/CT scan for liver malignancies, relative to routine (3D) F-18 FDG PET/CT scan. Materials and Methods This study presented a prospective clinical study of 16 patients who received F-18 FDG PET/CT scan for known or suspected malignant liver lesions. Ethics approvals were obtained from the ethics committees of the Hong Kong Baptist Hospital and The Hong Kong Polytechnic University. Liver lesions were compared between the gated and ungated image sets, in terms of 1) volume measurement of PET image, 2) accuracy of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and 3) accuracy of total lesion glycoses (TLG). Statistical analysis was performed by using a two-tailed paired Student t-test and Pearson correlation test. Results The study population consisted of 16 patients (9 males and 7 females; mean age of 65) with a total number of 89 lesions. The SUVmax and SUVmean measurement of the gated PET images was more accurate than that of the ungated PET images, compared to the static reference images. An average of 21.48% (p < 0.001) reduction of the tumor volume was also observed. The SUVmax and SUVmean of the gated PET images were improved by 19.81% (p < 0.001) and 25.53% (p < 0.001), compared to the ungated PET images. Conclusions We have demonstrated the feasibility of implementing 4D PET/CT scan for liver malignancies in a prospective clinical study. The 4D PET/CT scan for liver malignancies could improve the quality of PET image by improving the SUV accuracy of the lesions and reducing image blurring. The improved accuracy in the classification and identification of liver tumors with 4D PET image would potentially lead to its increased utilization in target delineation of GTV, ITV, and PTV for liver radiotherapy treatment planning in the future.
The Students’ Flow Experience With the Continuous Intention of Using Online English Platforms

Built on the integrated theoretical framework of antecedents of flow and expectation confirmation model (ECM), this research investigates the way flow experience drives the online students’ intention to engage in online English teaching platforms. This study focused on the online students engaged in online English learning platforms in Taiwan. A total of 500 online students were selected. An online survey was conducted with the help of a marketing research agency located in Taiwan. According to the results, the online students’ flow experience was found to be in a significant relationship with continuous intention. The antecedents, including perceived enjoyment, challenge, and situational involvement, were found to be in a positive relationship with flow experience; however, confirmation and perceived vividness did not have significant effects on the flow. Furthermore, flow and confirmation were found to be in a significant relationship with perceived usefulness and satisfaction. Moreover, perceived usefulness was found to be in a significant relationship with satisfaction and continuous intention. Lastly, satisfaction was found to be in a significant relationship with continuous intention. Finally, the questions proposed in this research with their empirical findings offer profound understanding for establishing a well-devised online English learning platform that can motivate online learning. These results and managerial implications for online English language platforms are innovative and significant in practice.
Amputation Predisposes to Higher Cancer-Specific Mortality Than Limb Salvage Surgery in Pediatric Patients With Osteosarcoma of the Limbs: A Propensity Matching Analysis

Objective With the development of osteosarcoma treatment, limb salvage surgery is gradually replacing amputation as the primary surgical option. Most pediatric osteosarcomas of the limbs undergo limb-salvage surgery. We aimed to use propensity score matching (PSM) analysis test the difference in cancer-specific mortality (CSM) between amputation and limb-salvage surgery in pediatric patients with Osteosarcoma of the limbs. PSM is a statistical method used to deal with data from an Observational Study. The PSM method is designed to reduce the influence of biases and confounding variables to make a more reasonable comparison between experimental and control groups. Methods Patient information was downloaded from the SEER (surveillance, epidemiology, and End Results) database from 2004 to 2018. We included all primary pediatric osteosarcoma patients who underwent limb salvage or amputation. Multivariate logistic regression models were used to explore the factors influencing patient choice of amputation. Differences in CSM and other causes of mortality (OSM) between limb salvage and amputation were analyzed using cumulative incidence plots and competitive risk regression tests after 1:1 proportional propensity score matching. Results A total of 1,058 pediatric patients with limbs Osteosarcoma were included. Patients who underwent amputations were more likely to be male (OR 1.4, P = 0.024) and more likely to have distant metastasis (OR 2.1, P < 0.001). Before propensity matching, CSM was 1.4 times higher in patients undergoing amputation than in patients undergoing limb salvage (P = 0.017) and 3.4 times higher in OSM (P = 0.007). After adjustment for propensity matching, CSM was 1.5 times higher in patients undergoing amputation than in patients undergoing limb salvage (P = 0.028), but there was no significant difference in OSM (HR 3.2, P = 0.078). Conclusions Our results suggested that amputation is associated with a 1.5-fold increase in CSM in pediatric patients with limbs Osteosarcoma. Therefore, in the surgical selection of pediatric patients with Osteosarcoma, limb salvage surgery should be the first choice in the absence of other contraindications.
Photoperiod Control of Plant Growth: Flowering Time Genes Beyond Flowering

Fluctuations in environmental conditions greatly influence life on earth. Plants, as sessile organisms, have developed molecular mechanisms to adapt their development to changes in daylength, or photoperiod. One of the first plant features that comes to mind as affected by the duration of the day is flowering time; we all bring up a clear image of spring blossom. However, for many plants flowering happens at other times of the year, and many other developmental aspects are also affected by changes in daylength, which range from hypocotyl elongation in Arabidopsis thaliana to tuberization in potato or autumn growth cessation in trees. Strikingly, many of the processes affected by photoperiod employ similar gene networks to respond to changes in the length of light/dark cycles. In this review, we have focused on developmental processes affected by photoperiod that share similar genes and gene regulatory networks.
Spatial Multiomics Analysis Reveals Only Minor Genetic and Epigenetic Changes in Human Liver Cancer Stem-Like Cells Compared With Other Tumor Parenchymal Cells

Cancer stem cells (CSCs) usually account for a very small tumor cell population but play pivotal roles in human cancer development and recurrence. A fundamental question in cancer biology is what genetic and epigenetic changes occur in CSCs. Here we show that the in-situ global levels of DNA cytosine modifications, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), are similar between liver cancer stem-like (LCSL) cells and paratumor liver cells of liver cancer patients. We then developed a robust method combining immunohistochemistry, laser capture microdissection and genome sequencing with ultra-low-input cells (CIL-seq) to study the detailed genetic and DNA methylation changes in human LCSL cells. We first used clinical samples of mixed hepatocellular carcinoma-cholangiocarcinoma (HCC-CCA) with stem cell features to investigate human LCSL cells. The CIL-seq analysis of HCC-CCA and HCC patients showed that LCSL cells had strong spatial genetic and epigenetic heterogeneity. More interestingly, although the LCSL cells had some potential key changes in their genome, they had substantially fewer somatic single nucleotide variants (SNVs), copy number alterations (CNAs) and differentially methylated regions than other tumor parenchymal cells. The cluster analysis of SNVs, CNAs, DNA methylation patterns and spatial transcriptomes all clearly showed that the LCSL cells were clustered with the paratumor liver cells. Thus, spatial multiomics analysis showed that LCSL cells had only minor genetic and epigenetic changes compared with other tumor parenchymal cells. Targeting key changes in CSCs, not just changes in bulk tumor cells, should be more effective for human cancer therapy.
Increased Levels of Interleukin-36 in Obesity and Type 2 Diabetes Fuel Adipose Tissue Inflammation by Inducing Its Own Expression and Release by Adipocytes and Macrophages

Interleukin (IL)-36 is a recently described cytokine with well-known functions in the regulation of multiple inflammatory diseases. Since no data exists on how this cytokine regulates adipose tissue (AT) homeostasis, we aimed to explore the function of a specific isoform, IL-36γ, an agonist, in human obesity and obesity-associated type 2 diabetes as well as in AT inflammation and fibrosis. Plasma IL-36γ was measured in 91 participants in a case-control study and the effect of weight loss was evaluated in 31 patients with severe obesity undergoing bariatric surgery. Gene expression levels of IL36G and its receptor were analyzed in relevant human metabolic tissues. The effect of inflammatory factors and IL-36γ was determined in vitro in human adipocytes and macrophages. We found, for the first time, that the increased (P<0.05) circulating levels of IL-36γ in patients with obesity decreased (P<0.001) after weight and fat loss achieved by Roux-en-Y gastric bypass and that gene expression levels of IL36G were upregulated in the visceral AT (P<0.05) and in the peripheral blood mononuclear cells (P<0.01) from patients with obesity. We also demonstrated increased (P<0.05) expression levels of Il36g in the epididymal AT from diet-induced obese mice. IL36G was significantly enhanced (P<0.001) by LPS in human adipocytes and monocyte-derived macrophages, while no changes were found after the incubation with anti-inflammatory cytokines. The addition of IL-36γ for 24 h strongly induced (P<0.01) its own expression as well as key inflammatory and chemoattractant factors with no changes in genes associated with fibrosis. Furthermore, adipocyte-conditioned media obtained from patients with obesity increased (P<0.01) the release of IL-36γ and the expression (P<0.05) of cathepsin G (CTSG) in monocyte-derived macrophages. These findings provide, for the first time, evidence about the properties of IL-36γ in the regulation of AT-chronic inflammation, emerging as a link between AT biology and the obesity-associated comorbidities.
Chemoresistance Transmission via Exosome-Transferred MMP14 in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. Gemcitabine is the most commonly used chemotherapy for the treatment of PDAC, but the development of drug resistance still remains challenging. Recently, exosomes have emerged as important mediators for intercellular communication. Exosomes affect recipient cells’ behavior through the engulfed cargos, however the specific cargos responsible for gemcitabine resistance in PDAC are poorly understood. Here, we reported that exosomes could transfer gemcitabine resistance via a metalloproteinase 14 (MMP14)-dependent mechanism. MMP14 was identified as a major differentially secreted protein from the gemcitabine-resistant PDAC cells by comparative secretome. It was packaged into the exosomes and transmitted from the chemoresistant cells to the sensitive ones. The exosome-transferred MMP14 could enhance drug resistance and promotes the sphere-formation and migration abilities of the recipient sensitive PDAC cells. Mechanically, exosome-transferred MMP14 promotes the stability of CD44, the cancer stem cell marker in the recipient cells. Our results indicate that MMP14 is a key player for exosome-mediated transfer of gemcitabine resistance, thus targeting MMP14 in exosomes may represent a novel strategy to limit gemcitabine resistance in PDAC.
Gated Recurrent Unit Coupled with Projection to Model Plane Imputation for the PM2.5 Prediction for Guangzhou City, China

Air pollution is generating serious health issues as well as threats to our natural ecosystem. Accurate prediction of PM2.5 can help taking preventive measures for reducing air pollution. The periodic pattern of PM2.5 can be modeled with recurrent neural networks to predict air quality. To the best of the author’s knowledge, very limited work has been conducted on the coupling of missing value imputation methods with gated recurrent unit (GRU) for the prediction of PM2.5 concentration of Guangzhou City, China. This paper proposes the combination of project to model plane (PMP) with GRU for the superior prediction performance of PM2.5 concentration of Guangzhou City, China. Initially, outperforming the missing value imputation method PMP is proposed for air quality data under consideration by making a comparison study on various methods such as KDR, TSR, IA, NIPALS, DA, and PMP. Secondly, it presents GRU in combination with PMP to show its superiority on other machine learning techniques such as LSSVM and two other RNN variants, LSTM and Bi-LSTM. For this study, data for Guangzhou City were collected from China’s governmental air quality website. Data contained daily values of PM2.5, PM10, O3, SOx, NOx, and CO. This study has employed RMSE, MAPE, and MEDAE as model prediction performance criteria. Comparison of prediction performance criteria on the test data showed GRU in combination with PMP has outperformed the LSSVM and other RNN variants LSTM and Bi-LSTM for Guangzhou City, China. In comparison with prediction performance of LSSVM, GRU improved the prediction performance on test data by 40.9% RMSE, 48.5% MAPE, and 50.4% MEDAE.
Precipitation Alters the Effects of Temperature on the Ecosystem Multifunctionality in Alpine Meadows

Precipitation and temperature are major controls on multiple ecosystem functions in alpine grasslands. There is scant evidence for the interactive effects of temperature and precipitation changes on the ecosystem multifunctionality (EMF) in alpine meadows. To explore the interactive effects of temperature and precipitation changes on the EMF in alpine meadows, we transplanted meadow blocks reciprocally among three altitudes (4,650, 4,950, and 5,200 m) on the central Tibetan Plateau. Compared with the home sites (control), the EMF has a trend to increase when meadow blocks were downward transplanted (experimental warming) to the high-precipitation sites but decrease as meadow blocks were downward transplanted to the low-precipitation sites. However, the experimental cooling (upward transplantation) consistently reduced the EMF regardless of the precipitation change. The increase of EMF under the experimental warming was closely related to the variation of both plant and soil functions, whereas the reduction of EMF under the cooling was highly correlated with the decrease of plant function. Our results highlight that climate warming effects on the EMF are greatly associated with precipitation changes in the semi-arid alpine ecosystems.