Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in chemical and biological characterization of triterpenoid saponins from Anagallis arvensis L. using UHPLC-MS/MS and cell-based assays

Abstract A fraction enriched in triterpenoid saponins (F4) from Anagallis arvensis L. was chemically characterized by UHPLC-ESI-QTOF-MS/MS and NMR analyses. The results proposed the presence of nine monodesmosidic saponins derived from oleanolic acid, including two reported for the first time for this species, 3: 3-O-{β-D-glucopyranosyl (1→4)-[β-D-xylopyranosyl (1→2)]-β-D-glucopyranosyl (1→4)-[β-D-glucopyranosyl (1→2)]-α-L-arabinopyranosyl}-13β, 28-epoxy- 22 acetyl- 28 methoxy-16α, 24-oleananediol and 4: 3-O-{β-D-glucopyranosyl (1→4)-β-D-glucopyranosyl (1→4)-[β-D-xylopyranosyl (1→2)]-β-D-glucopyranosyl (1→4)-[β-D-glucopyranosyl (1→2)]-α-L-arabinopyranosyl}-13β, 28-epoxy- 16α, 30-oleananediol. Furthermore, haemolytic activity was determined by dot-blot autography, and cytotoxicity on human lymphocyte cultures was analysed according to metabolic activity (MTT assay) and membrane integrity (Trypan blue exclusion test). F4 showed mild cytotoxicity (%V > 50% at 100 μg/mL) on human lymphocytes under conditions of activation or not by LPS; moreover, showed haemolytic activity between 50 and 500 μg. This work contributed to phytochemical knowledge of the triterpenoid saponins from A. arvensis, and its cytotoxic effects on normal human cells. Graphical Abstract
Preclinical Comparison of Distal Off-Pump Anastomotic Remodeling: Hand-Sewn Versus ELANA Heart Bypass

Objective: The ELANA Heart Bypass System is a new sutureless technique for coronary anastomoses. A titanium clip connects the graft with the coronary artery, whereafter the arteriotomy is performed by excimer laser. Since this anastomotic construction evidently differs from the standard hand-sewn anastomosis, we aim to evaluate the process of anastomotic healing and remodeling. Methods: Preclinical evaluation of anastomotic remodeling in 42 pigs who underwent off-pump left internal mammary artery to left anterior descending artery anastomosis by either the ELANA Heart Bypass (n = 24) or the hand-sewn (n = 18) technique. Anastomotic remodeling was evaluated by scanning electron microscopy and histology in short-term follow-up intervals up to 3 months. Anastomotic patency is determined by coronary angiography at latest follow-up before termination. Results: The nonendothelial surface of both the ELANA and the hand-sewn anastomoses were covered with neointima from 14 days onwards. Only half the amount of intima hyperplasia was present in the anastomotic surface of the patent ELANA anastomosis, compared with the hand-sewn anastomosis (98 [48–1358] vs 218 [108–296] µm, P = 0.001). Yet patency of the ELANA was inferior to the hand-sewn anastomoses (79% vs 100%, P = 0.06). Conclusions: This study shows the technical perioperative feasibility of the ELANA Heart Bypass System. Although limited intima hyperplasia was observed, hand-sewn anastomoses had superior patency during follow-up. The results of this trial suggest that an additional study with a new prototype is required before clinical implementation.
Leisure-time physical activity in Amazonian pregnant women and offspring birth weight: A prospective cohort study

Compelling evidence supports the current international recommendation of at least 150 min/week of leisure-time physical activity (LTPA) during pregnancy. However, the potential relationship between LTPA and birth weight (BW) remains unclear in low- and middle-income countries. The purpose of this study was to examine the association between LTPA during pregnancy and offspring BW in an Amazonian population. Prospective cohort study was carried-out with 500 pregnant women and their offspring followed-up in the MINA-Brazil study, which was conducted in Cruzeiro do Sul, Western Brazilian Amazon. LTPA was assessed in the second (mean 19.6, SD 2.4 weeks) and third (mean 27.8, SD 1.6 weeks) gestational trimesters by a standardised interview and categorised according to the recommended cut-off of at least 150 min/week. We calculated offspring BW z-scores by sex and gestational age. We then explored the effect of LTPA during pregnancy on offspring BW, the association between LTPA and small-for-gestational-age (SGA) or large-for-gestational-age (LGA) births, and the mediating role of excessive and insufficient gestational weight gain (GWG). At least 150 min/week of LTPA during the third gestational trimester was associated with an offspring BW decrease of -0.35 z-score (95% CI: -0.65, -0.05) or -147.9 grams (95% CI: -260.9, -14.8), without increasing the frequency of SGA foetuses either in the second or third gestational trimester (p > 0.05). Excessive GWG mediated the effect of LTPA on the offspring BW (indirect effect = -0.05 z-score [95% CI: -0.10, -0.00] or -34.7 grams (95% CI: -66.1, -3.3]). This mediation effect was not observed for insufficient GWG. LTPA in the third, but not in the second, trimester of pregnancy was inversely associated with offspring BW without increasing the frequency of SGA, an effect that was partly mediated by excessive GWG.
18F-FSPG PET imaging for the evaluation of indeterminate pulmonary nodules

Background 18F-fluorodeoxyglucose (FDG) PET/CT is recommended for evaluation of intermediate-risk indeterminate pulmonary nodules (IPNs). While highly sensitive, the specificity of FDG remains suboptimal for differentiating malignant from benign nodules, particularly in areas where fungal lung diseases are prevalent. Thus, a cancer-specific imaging probe is greatly needed. In this study, we tested the hypothesis that a PET radiotracer (S)-4-(3-[18F]-fluoropropyl)-L-glutamic acid (FSPG) improves the diagnostic accuracy of IPNs compared to 18F-FDG PET/CT. Methods This study was conducted at a major academic medical center and an affiliated VA medical center. Twenty-six patients with newly discovered IPNs 7-30mm diameter or newly diagnosed lung cancer completed serial PET/CT scans utilizing 18F-FDG and 18F-FSPG, without intervening treatment of the lesion. The scans were independently reviewed by two dual-trained diagnostic radiology and nuclear medicine physicians. Characteristics evaluated included quantitative SUVmax values of the pulmonary nodules and metastases. Results A total of 17 out of 26 patients had cancer and 9 had benign lesions. 18F-FSPG was negative in 6 of 9 benign lesions compared to 7 of 9 with 18F-FDG. 18F-FSPG and 18F-FDG were positive in 14 of 17 and 12 of 17 malignant lesions, respectively. 18F-FSPG detected brain and intracardiac metastases missed by 18F-FDG PET in one case, while 18F-FDG detected a metastasis to the kidney missed by 18F-FSPG. Conclusion In this pilot study, there was no significant difference in overall diagnostic accuracy between 18F-FSPG and 18F-FDG for the evaluation of IPNs and staging of lung cancer. Additional studies will be needed to determine the clinical utility of this tracer in the management of IPNs and lung cancer.
Ghrelin Relieves Obesity-Induced Myocardial Injury by Regulating the Epigenetic Suppression of miR-196b Mediated by lncRNA HOTAIR

Introduction: Obesity has been believed to be closely linked with many kinds of diseases including atherosclerosis, hypertension, cerebrovascular thrombosis, and diabetes. Ghrelin and Homeobox transcript antisense RNA (HOTAIR) were believed to be involved in the regulation of myocardial injury. Methods: The obesity mice model was established through feeding mice (C57BL/6J, male, eight-week-old) with high-fat diet and palmitate (PA)-induced cardiomyocyte injury. RNA and protein levels were detected with Quantitative real-time PCR and Western blotting. The levels of TG, TCH, LDL, CK-MB, cTnl, and BNP in the serum or cell medium supernatant were measured using ELISA kits. The ROS level was detected with the DCFH-DA method. Binding sites between different targets were identified using detection of dual luciferase reporter assay. Cell apoptosis was analyzed by flow cytometry. RNA-binding protein immunoprecipitation and chromatin immunoprecipitation were used to detect the binding of DNMT3B with HOTAIR or miR-196b promoter. Results: The expression of HOTAIR was downregulated, and miR-196b was upregulated in the obese myocardial injury. Ghrelin attenuated PA-induced cardiomyocyte injury by increasing HOTAIR. HOTAIR regulated the expression of miR-196b by recruiting DNMT3B to induce methylation of the miR-196b gene promoter. The binding site between miR-196b and IGF-1 was identified. Discussion/Conclusion: We demonstrated that ghrelin attenuated PA-induced cardiomyocyte injury by regulating the HOTAIR/miR-196b/IGF-1 signaling pathway. Our findings might provide novel thought for the prevention and treatment of obesity-induced myocardial injury by targeting HOTAIR/miR-196b.
The roles of implicit approach motivation and explicit reward in excessive and problematic use of social networking sites

Despite growing concerns about the addictive potential of social networking sites (SNSs), little is known about the precise neural, cognitive, and emotional processes underpinning compulsive SNS behaviours, such as excessive checking of SNSs. Recent evidence points to the important role of reward in SNS behaviours and one avenue to examine reward processes related to SNSs is the use of behavioural paradigms that allow for the measurement of implicit motivational responses, such as the approach avoidance task (AAT). The AAT has been successfully utilised to capture changes in unconscious reward processes in substance use disorders and other behavioural addictions, with faster approach reactions to addiction-related stimuli reflecting increased wanting/urges to have/consume the reward. In the present study 411 young adults completed an online Visual Approach/Avoidance by the Self Task (VAAST) with social media and control logos as well as other subjective (explicit) measures of reward experience related to SNSs. Our results showed that across participants SNS logos elicited strong approach reactions (compared to control stimuli) and that stronger SNS approach tendencies predicted more frequent SNS checking. Importantly, increased approach motivation was not associated with more problematic use. However, both checking frequency and problematic use were related to alterations of explicit reward processing, including the subjective experience of SNS urges or wanting. We conclude that changes in automatic approach motivation towards SNS stimuli are common in most SNS users, which suggests that implicit imbuement of social media with reward has become pervasive among young adults. Problematic SNS use however may be more reliably indicated by changes in explicit reward processing, such as subjective wanting.
Complete Coding Sequence of Lumpy Skin Disease Virus Isolated from Kinmen Island, Taiwan, in 2020

We reported the complete coding sequence of a lumpy skin disease virus (LSDV) isolated from cattle from Kinmen, Taiwan, in 2020. The nucleotide sequence of LSDV/KM/Taiwan/2020 was most closely related to strains from an outbreak in China and Vietnam in 2020 and clustered within the vaccine or vaccine-derived clade. ABSTRACT We reported the complete coding sequence of a lumpy skin disease virus (LSDV) isolated from cattle from Kinmen, Taiwan, in 2020. The nucleotide sequence of LSDV/KM/Taiwan/2020 was most closely related to strains from an outbreak in China and Vietnam in 2020 and clustered within the vaccine or vaccine-derived clade.
Double-layered hand-sewn anastomosis: a valuable resource for the colorectal surgeon

Hand-sewn anastomosis is an essential and fundamental skill for surgeons dealing with any gastrointestinal anastomosis. Despite the advances in minimally invasive surgery and stapling devices, there are still complex surgical circumstances when the surgeon’s surgical know-how are necessary. Therefore, a safe hand-sewn technique for bowel anastomosis is required to establish a tension-free, well-perfused, and sealed anastomosis that allows gastrointestinal continuity with no unexpected complications. We describe a step-by-step procedure for hand-sewn double-layered anastomosis that reflects these principles and is practical for small and large bowel anastomosis.
Utilization of Machine Learning for the Differentiation of Positional NPS Isomers with Direct Analysis in Real Time Mass Spectrometry

The differentiation of positional isomers is a well established analytical challenge for forensic laboratories. As more novel psychoactive substances (NPSs) are introduced to the illicit drug market, robust yet efficient methods of isomer identification are needed. Although current literature suggests that Direct Analysis in Real Time–Time-of-Flight mass spectrometry (DART-ToF) with in-source collision induced dissociation (is-CID) can be used to differentiate positional isomers, it is currently unclear whether this capability extends to positional isomers whose only structural difference is the precise location of a single substitution on an aromatic ring. The aim of this work was to determine whether chemometric analysis of DART-ToF data could offer forensic laboratories an alternative rapid and robust method of differentiating NPS positional ring isomers. To test the feasibility of this technique, three positional isomer sets (fluoroamphetamine, fluoromethamphetamine, and methylmethcathinone) were analyzed. Using a linear rail for consistent sample introduction, the three isomers of each type were analyzed 96 times over an eight-week timespan. The classification methods investigated included a univariate approach, the Welch t test at each included ion; a multivariate approach, linear discriminant analysis; and a machine learning approach, the Random Forest classifier. For each method, multiple validation techniques were used including restricting the classifier to data that was only generated on one day. Of these classification methods, the Random Forest algorithm was ultimately the most accurate and robust, consistently achieving out-of-bag error rates below 5%. At an inconclusive rate of approximately 5%, a success rate of 100% was obtained for isomer identification when applied to a randomly selected test set. The model was further tested with data acquired as a part of a different batch. The highest classification success rate was 93.9%, and error rates under 5% were consistently achieved.
Seizure Types Classification by Generating Input Images With in-Depth Features From Decomposed EEG Signals for Deep Learning Pipeline

Electroencephalogram (EEG) based seizure types classification has not been addressed well, compared to seizure detection, which is very important for the diagnosis and prognosis of epileptic patients. The minuscule changes reflected in EEG signals among different seizure types make such tasks more challenging. Therefore, in this work, underlying features in EEG have been explored by decomposing signals into multiple subcomponents which have been further used to generate 2D input images for deep learning (DL) pipeline. The Hilbert vibration decomposition (HVD) has been employed for decomposing the EEG signals by preserving phase information. Next, 2D images have been generated considering the first three subcomponents having high energy by involving continuous wavelet transform and converting them into 2D images for DL inputs. For classification, a hybrid DL pipeline has been constructed by combining the convolution neural network (CNN) followed by long short-term memory (LSTM) for efficient extraction of spatial and time sequence information. Experimental validation has been conducted by classifying five types of seizures and seizure-free, collected from the Temple University EEG dataset (TUH v1.5.2). The proposed method has achieved the highest classification accuracy up to 99% along with an F1-score of 99%. Further analysis shows that the HVD-based decomposition and hybrid DL model can efficiently extract in-depth features while classifying different types of seizures. In a comparative study, the proposed idea demonstrates its superiority by displaying the uppermost performance.
Vortex dynamics simulation for pinning structure optimization in the applications of high-temperature superconductors

We introduce a molecular dynamics based simulation model that enables the efficient optimization of complex pinning structures in unpresented wide magnetic field and angular ranges for high-temperature superconductor applications. The fully three-dimensional simulation allows the modeling of the critical current and the associated anisotropy in the presence of any kinds of defects despite their size and orientation. Most prominently, these include artificial defects such as nanorods along with intrinsic weak-links or ab-plane oriented stacking faults, for example. In this work, we present and analyze the most fundamental results of the simulation model and compare them indirectly with a wide range of previous experimental and computational observations. With the provided validation for the proposed simulation model, we consider it to be an extremely useful tool in particular for pushing the limits of ampacity in the coated conductor industry.
Transcription pattern of key molecular chaperones in heat shocked caprine cardiac fibroblasts

Abstract The present study was attempted to unveil the impact of heat stress on transcription pattern of major heat shock response genes in caprine cardiac fibroblasts. Cardiac tissues (n = 6) were collected and primary cardiac cell culture was done. Cultured cardiac fibroblasts were kept in an atmosphere of 5% CO2 and 95% air at 38.5 °C. Cardiac cells achieved 70-75% confluence after 72 hours of incubation. Heat stress was induced on confluent cardiac fibroblasts at 42 °C for 0 (control), 20, 60, 100 and 200 min. Quantitative RT-PCR for β2m (internal control), HSP60, HSP70, HSP90, and HSP110 was done and their transcription pattern was assessed by Pfaffl method. HSP60, HSP90, and HSP110 transcription did not differ at 20 min, up-regulated (p < 0.05) from 60 to 200 min and registered highest at 200 min of heat exposure. HSP70 transcription was gradually escalated (p < 0.05) time dependently from 20 to 200 min and reached zenith at 200 min of heat exposure. Differential induction in transcription of key molecular chaperones at various durations of heat exposure might reduce cardiac fibroblasts apoptosis and thus could maintain cardiac tissue function during heat stress.
Algorithm to Identify Incident Epithelial Ovarian Cancer Cases Using Claims Data

PURPOSE To create an algorithm to identify incident epithelial ovarian cancer cases in claims-based data sets and evaluate performance of the algorithm using SEER-Medicare claims data. METHODS We created a five-step algorithm on the basis of clinical expertise to identify incident epithelial ovarian cancer cases using claims data for (1) ovarian cancer diagnosis, (2) receipt of platinum-based chemotherapy, (3) no claim for platinum-based chemotherapy but claim for tumor debulking surgery, (4) removed cases with nonplatinum chemotherapy, and (5) removed patients with prior claims with personal history of ovarian cancer code to exclude prevalent cases. We evaluated algorithm performance using SEER-Medicare claims data by creating four cohorts: incident epithelial ovarian cancer, a 5% random sample of cancer-free Medicare beneficiaries, a 5% random sample of incident nonovarian cancer, and prevalent ovarian cancer cases. RESULTS Using SEER tumor registry data as the gold standard, our algorithm correctly classified 89.9% of incident epithelial ovarian cancer cases (cohort n = 572) and almost 100% of cancer-free controls (n = 97,127), nonovarian cancer (n = 714), and prevalent ovarian cancer cases (n = 3,712). The overall algorithm sensitivity was 89.9%, the positive predictive value was 93.8%, and the specificity and negative predictive value were > 99.9%. Patients were more likely to be correctly classified as incident ovarian cancer if they had stage III or IV disease compared with early stage I or II disease (93.5% v 83.7%, P < .01), and grade 1-4 compared with unknown grade tumors (93.8% v 81.4%, P < .01). CONCLUSION Our algorithm correctly identified most incident epithelial ovarian cancer cases, especially those with advanced disease. This algorithm will facilitate research in other claims-based data sets where cancer registry data are unavailable.
Metabolic adaptation of ovarian tumors in patients treated with an IDO1 inhibitor constrains antitumor immune responses

To uncover underlying mechanisms associated with failure of indoleamine 2,3-dioxygenase 1 (IDO1) blockade in clinical trials, we conducted a pilot, window-of-opportunity clinical study in 17 patients with newly diagnosed advanced high-grade serous ovarian cancer before their standard tumor debulking surgery. Patients were treated with the IDO1 inhibitor epacadostat, and immunologic, transcriptomic, and metabolomic characterization of the tumor microenvironment was undertaken in baseline and posttreatment tumor biopsies. IDO1 inhibition resulted in efficient blockade of the kynurenine pathway of tryptophan degradation and was accompanied by a metabolic adaptation that shunted tryptophan catabolism toward the serotonin pathway. This resulted in elevated nicotinamide adenine dinucleotide (NAD+), which reduced T cell proliferation and function. Because NAD+ metabolites could be ligands for purinergic receptors, we investigated the impact of blocking purinergic receptors in the presence or absence of NAD+ on T cell proliferation and function in our mouse model. We demonstrated that A2a and A2b purinergic receptor antagonists, SCH58261 or PSB1115, respectively, rescued NAD+-mediated suppression of T cell proliferation and function. Combining IDO1 inhibition and A2a/A2b receptor blockade improved survival and boosted the antitumor immune signature in mice with IDO1 overexpressing ovarian cancer. These findings elucidate the downstream adaptive metabolic consequences of IDO1 blockade in ovarian cancers that may undermine antitumor T cell responses in the tumor microenvironment. Description IDO1 blockade leads to metabolic adaptation of ovarian tumors and increased NAD+, resulting in immune suppression in the tumor microenvironment. Saying “I DO” to combination therapy Indoleamine 2,3-dioxygenase 1 (IDO1) drives immunosuppression in high-grade serous ovarian cancer. Inhibition of IDO1 in combination with chemotherapy has shown limited efficacy in clinical trials. Here, Odunsi et al. treated patients with the IDO1 inhibitor epacadostat and studied the effect on the tumor microenvironment (TME) in tumor biopsies. IDO1 inhibition increased nicotinamide adenine dinucleotide (NAD+), which reduced T cell function in the TME. Combining epacadostat with purinergic receptor antagonists rescued T cell proliferation in a mouse model of ovarian cancer. These findings highlight the potential downside of IDO1 inhibition and suggest that IDO1 inhibitor therapy will require combination with NAD+ signaling blockade.