Miracle-dz/UniFAR-FTUs huggingface dataset:
Triptolide inhibits migration and proliferation of fibroblasts from ileocolonic anastomosis of patients with Crohn's disease via regulating the miR-16-1/HSP70 pathway

Anastomotic fibrosis is highly likely to lead to reoperation in Crohn's disease (CD) patients. Triptolide (TPL) is considered to have anti-inflammatory and antifibrotic effects in a variety of autoimmune diseases, including CD. The present study aimed to investigate the effects of TPL on fibroblasts from strictured ileocolonic anastomosis of patients with CD and its underlying mechanism. Primary fibroblasts were obtained from strictured anastomosis tissue (SAT) samples and matched anastomosis-adjacent normal tissue (NT) samples which were collected from 10 CD patients who underwent reoperation because of anastomotic stricture. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure miR-16-1 and heat shock protein 70 (HSP70) levels. Western blotting was conducted to determine expression of HSP70, collagen I (Col-I), collagen III (Col-III) and α-smooth muscle actin (α-SMA) proteins. Agomir-16-1 and antagomir-16-1 were used to up and downregulate the expression of miR-16-1, respectively. Small interfering RNA (siRNA) was employed to inhibit the expression of HSP70. A wound healing assay was performed to measure the migration of fibroblasts. Cell proliferation was evaluated by MTT and 5-bromo-2-deoxyrudidine assays. Cell apoptosis was determined by caspase-3 activity and TUNEL assays. The results demonstrated that the levels of Col-I, Col-III and α-SMA were all significantly upregulated in SAT compared with NT. miR-16-1 levels in the SAT group were significantly compared with the NT group; conversely, the expression levels of HSP70 mRNA and protein in the SAT group were significantly lower compared with the NT group. Next, fibroblasts were treated with TPL to examine its effect on the miR-16-1/HSP70 pathway. The results demonstrated that the elevated expression of miR-16-1 in the SAT group was effectively inhibited by TPL treatment. Compared with the NT group, both the mRNA and protein levels of HSP70 were significantly downregulated in the SAT group cells, while TPL exhibited a strong promoting effect on HSP70 synthesis. Furthermore, upregulation of miR-16-1 reversed the effect of TPL on the miR-16-1/HSP70 pathway in fibroblasts from SAT. Overexpression of miR-16-1 significantly reversed the inhibitory effects of TPL treatment on migration, proliferation and extracellular matrix (ECM)-associated protein expression of fibroblasts from SAT. Finally, downregulation of miR-16-1 caused similar effects to the fibroblasts as the TPL treatment; however, the inhibitory effects on cell biological functions induced by antagomir-16-1 were all significantly reversed by HSP70 silencing. The present findings indicated that TPL may be a potential therapeutic option for postoperative anastomosis fibrosis of patients with CD. The miR-16-1/HSP70 pathway had a substantial role in the inhibitory effects of TPL on migration, proliferation and ECM synthesis rate of fibroblasts from strictured anastomosis tissues.
Milestones in Personalized Medicine: From the Ancient Time to Nowadays—the Provocation of COVID-19

The first evidence of individual targeting medicine appeared in ancient times thousands of years ago. Various therapeutic approaches have been established since then. However, even nowadays, conventional therapies do not take into consideration individuals' idiosyncrasy and genetic make-up, failing thus to be effective in some cases. Over time, the necessity of a more precise and effective treatment resulted in the development of a scientific field currently known as “personalized medicine. ” The numerous technological breakthroughs in this field have acknowledged personalized medicine as the next generation of diagnosis and treatment. Although personalized medicine has attracted a lot of attention the last years, there are still several obstacles hindering its application in clinical practice. These limitations have come to light recently, due to the COVID-19 pandemic. This review describes the “journey” of personalized medicine over time, emphasizing on important milestones achieved through time. Starting from the treatment of malaria, as a first more personalized therapeutic approach, it highlights the need of new diagnostic tools and therapeutic regimens based on individuals' genetic background. Furthermore, it aims at raising global awareness regarding the current limitations and the necessity of a personalized strategy to overpass healthcare problems and hence, the current crisis.
Factors That Influence Confirmation of Neisseria gonorrhoeae Positivity by Molecular Methods

Several Neisseria gonorrhoeae nucleic acid amplification tests (NAATs) with high sensitivity exist. However, the specificity of N. gonorrhoeae NAATs may be suboptimal, particularly for extragenital biospecimens. ABSTRACT Several Neisseria gonorrhoeae nucleic acid amplification tests (NAATs) with high sensitivity exist. However, the specificity of N. gonorrhoeae NAATs may be suboptimal, particularly for extragenital biospecimens. Consequently, confirmation with a second NAAT is common, although this represents a burden on resources. Furthermore, the rationale for confirmation is contentious. The objective of this work was to assess N. gonorrhoeae confirmation in over 13,000 N. gonorrhoeae screen-positive samples representing various biospecimens and three separate screening assays, the Abbott RealTime CT/NG (Abbott Molecular, Inc., Des Plaines, IL), the Cobas CT/NG test (Roche Molecular Systems Inc., Alameda, CA), and the BD ProbeTec ET CT/GC amplified DNA assay (BD Diagnostics, Sparks, MD). Factors predictive of confirmation were determined via logistic regression involving sex, year, whether the sample was formally validated, and sample site. Level of confirmation varied according to screening assay (96.2%, 86.0%, and 73.9% for the Abbott, Roche, and BD tests, respectively) in sample types formally included according to the manufacturers’ instructions (i.e., validated). Sex did not affect confirmation for 2/3 assays, and the likelihood of confirmation of samples not formally included in manufacturer instructions (i.e., nonvalidated) was 89.1%, 82.1%, and 59.2% for the Abbott, Roche, and BD tests, respectively. Rectal swabs, which are nonvalidated samples, confirmed in 91.5%, 90.1%, and 87.4% of samples initially tested with the respective assays. The requirement to confirm N. gonorrhoeae in validated samples is not required for all NAATs, although initial assay-specific evaluation is justified given observed variability. Rectal samples represent robust biospecimens for N. gonorrhoeae NAAT testing and may not require confirmation when screened with the assays described.
Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer’s Disease

Background Individuals with Alzheimer’s Disease (AD) are often characterized by systemic markers of insulin resistance; however, the broader effects of AD on other relevant metabolic hormones, such as incretins that affect insulin secretion and food intake, remains less clear. Methods Here, we leveraged a physiologically relevant meal tolerance test to assess diagnostic differences in these metabolic responses in cognitively healthy older adults (CH; n = 32) and AD (n = 23) participants. All individuals also underwent a comprehensive clinical examination, cognitive evaluation, and structural magnetic resonance imaging. Results The meal-stimulated response of glucose, insulin, and peptide tyrosine tyrosine (PYY) was significantly greater in individuals with AD as compared to CH. Voxel-based morphometry revealed negative relationships between brain volume and the meal-stimulated response of insulin, C-Peptide, and glucose-dependent insulinotropic polypeptide (GIP) in primarily parietal brain regions. Conclusion Our findings are consistent with prior work that shows differences in metabolic regulation in AD and relationships with cognition and brain structure.
An Information-based Model for Writing Style Analysis of Lyrics

One of the most important parts of the song’s content is the lyrics, in which authors expose feelings or thoughts that may reﬂect their way of seeing the world. This is perhaps the reason why modern techniques of mining text have been applied to lyrics to ﬁnd semantic aspects that allow us to recognize emotions, topics, authorship among others. In this work, we focus on the analysis of syntactic aspects assuming that they are important elements to recognize patterns related to the writing style of an individual author or a musical genre. We present a theoretical information model-based in a corpus of lyrics, which allows ﬁnding discriminating elements in a writing style that could be used to estimate, for example, the authorship or musical genre of a given lyric.
Analyses of predictive factors for pathological complete remission in neoadjuvant therapy for locally advanced rectal cancer.

PURPOSE To analyze relevant factors for pathological complete remission (pCR) after neoadjuvant therapy for locally advanced rectal cancer. METHODS The clinical data of 531 patients with the American Joint Committee on Cancer (AJCC) stage II or III rectal cancer from January 2014 to December 2017 were retrospectively analyzed. Among these patients, 100 (18.83%) patients achieved pCR. Univariate and multivariate logistic regression analyses were applied to analyze the predictive factors for pCR after neoadjuvant therapy. RESULTS According to univariate analysis, carcinoembryonic antigen (CEA) before chemo-radiotherapy (CRT) (p=0.021), tumor (T) stage before CRT (p=0.002), interval between the end of CRT and surgery (p<0.001) and maximum depth of tumor invasion before CRT (p=0.039) influenced significantly pCR. Multivariate analysis manifested that the CEA level before CRT [p=0.037, odds ratio (OR) =0.435] and the interval between the end of CRT and surgery (p=0.004, OR=2.864) were significant predictive factors for pCR. Stratified analysis showed that low-level CEA before CRT (p=0.029) affected pCR only in non-smoking group. CONCLUSIONS pCR can be observed in some patients with locally advanced rectal cancer after neoadjuvant therapy. Low-level CEA before CRT and long interval between CRT and surgery are predictive factors for pCR of preoperative neoadjuvant therapy for locally advanced rectal cancer, but low-level CEA is effective in predicting pCR in non-smokers only.
Transcranial Direct Current Stimulation to Enhance Cognitive Impairment in Parkinson's Disease: A Systematic Review and Meta-Analysis

Cognitive deficits are increasingly being recognized as a common trait in Parkinson's disease (PD). Recently, transcranial direct current stimulation (tDCS) has been shown to exert positive effects as an adjunctive therapy on motor and non-motor symptoms in PD. This systematic review and meta-analysis aims to provide an overview of reported evidence on the efficacy of tDCS interventions in the treatment of cognitive impairments in PD. A systematic literature review was conducted to examine articles that were published in the past 10 years and that study the effects of tDCS on cognitive deficits in PD patients. The PubMed, Scopus and Scielo databases were searched. Eight tDCS studies involving 168 participants were included for the analysis. Our meta-analysis results showed that anodal tDCS (atDCS) had various levels or no evidence of effectiveness. In the pre-post stimulation analysis, a strong effect was reported for executive functions (pre-post: g = 1.51, Z = 2.41, p = 0.016); non-significant effects were reported for visuospatial skills (pre-post: g = 0.27, Z = 0.69, p = 0.490); attention (pre-post: g = 0.02, Z = 0.08, p = 0.934), memory (pre-post: g = 0.01, Z = 0.03, p = 0.972) and language (pre-post: g = 0.07, Z = 0.21, p = 0.832). However, in the pre-follow-up stimulation analysis, the duration of the effect was not clear. This study highlights the potential effectiveness of atDCS to improve cognitive performance in PD patients but failed to establish a cause-effect relationship between tDCS intervention and cognitive improvement in PD. Future directions and recommendations for methodological improvements are outlined.
A Deep Learning-Based Approach for Identifying the Medicinal Uses of Plant-Derived Natural Compounds

Medicinal plants and their extracts have been used as important sources for drug discovery. In particular, plant-derived natural compounds, including phytochemicals, antioxidants, vitamins, and minerals, are gaining attention as they promote health and prevent disease. Although several in vitro methods have been developed to confirm the biological activities of natural compounds, there is still considerable room to reduce time and cost. To overcome these limitations, several in silico methods have been proposed for conducting large-scale analysis, but they are still limited in terms of dealing with incomplete and heterogeneous natural compound data. Here, we propose a deep learning-based approach to identify the medicinal uses of natural compounds by exploiting massive and heterogeneous drug and natural compound data. The rationale behind this approach is that deep learning can effectively utilize heterogeneous features to alleviate incomplete information. Based on latent knowledge, molecular interactions, and chemical property features, we generated 686 dimensional features for 4,507 natural compounds and 2,882 approved and investigational drugs. The deep learning model was trained using the generated features and verified drug indication information. When the features of natural compounds were applied as input to the trained model, potential efficacies were successfully predicted with high accuracy, sensitivity, and specificity.
Microplastic Exposure by Razor Clam Recreational Harvester-Consumers Along a Sparsely Populated Coastline

Microplastics (MPs) are anthropogenic contaminants found in coastal and marine environments worldwide. Pacific razor clams (Siliqua patula), important for local indigenous culture, economy, gastronomy and food security along the United States West Coast, are subjected to myriad environmental stressors including predation, storm events, disease, toxins, and MPs. This study aimed to determine MP burdens in Olympic Coast, Washington Pacific razor clams and estimate annual MP exposure of recreational razor clam harvester-consumers from eating this species. We quantified suspected MP burdens in Pacific razor clams collected from eight tribal, recreational, and commercial harvest areas on the Olympic Coast in April 2018. We administered questionnaires to 107 recreational razor clam harvesters during the same timeframe to determine consumption patterns, preparation styles, knowledge and concerns about MPs, and demographics. Razor clams containing suspected MPs, primarily microfibers, were found at all eight sites. Average suspected MP burden differed by sample type (whole = 6.75 ± 0.60, gut-tissue = 7.88 ± 0.71, non-gut tissue = 4.96 ± 0.56, and cleaned samples = 3.44 ± 0.25). FTIR analyses of a random subset of microfiber-type MPs in whole and cleaned clams indicated material types of polyethylene terephthalate, cellulose acetate, cellophane, polyester, nylon, and cellulose. The average number of razor clams consumed per meal by Olympic Coast recreational razor clam harvesters was 4.27 ± 0.27, which varied by gender and ethnicity, but not income or age. Harvesters ate 0–209 meals/year of razor clams (16.2% harvested but did not eat razor clams), and most respondents (88.3%) fully cleaned razor clams before consuming them. Annual suspected MP exposure for razor clam harvester-consumers was 60–3,070 for cleaned and 120–6,020 for whole clams. Our findings suggest Olympic Coast recreational razor clam harvester-consumers are exposed to low levels of MPs from eating razor clams. MP exposure can be reduced by roughly 50% if clams are cleaned before consumption. Our work serves as an important reference in the growing portfolio of Pacific Northwest microplastic research, to inform future MP attenuation recommendations and development of human health standards for this type of pollution.
Hypoxia Shapes Autophagy in LPS-Activated Dendritic Cells

During their lifespan, dendritic cells (DCs) are exposed to different pO2 levels that affect their differentiation and functions. Autophagy is one of the adaptive responses to hypoxia with important implications for cell survival. While the autophagic machinery in DCs was shown to impact signaling of TLRs, its regulation by the MD-2/TLR4 ligand LPS is still unclear. The aim of this study was to evaluate whether LPS can induce autophagy in DCs exposed to either aerobic or hypoxic conditions. Using human monocyte-derived DCs and the combination of immunofluorescence confocal analysis, measure of mitochondrial membrane potential, Western blotting, and RT-qPCR, we showed that the ability of LPS to modulate autophagy was strictly dependent upon pO2 levels. Indeed, LPS inhibited autophagy in aerobic conditions whereas the autophagic process was induced in a hypoxic environment. Under hypoxia, LPS treatment caused a significant increase of functional lysosomes, LC3B and Atg protein upregulation, and reduction of SQSTM1/p62 protein levels. This selective regulation was accompanied by activation of signalling pathways and expression of cytokines typically associated with DC survival. Bafilomycin A1 and chloroquine, which are recognized as autophagic inhibitors, confirmed the induction of autophagy by LPS under hypoxia and its impact on DC survival. In conclusion, our results show that autophagy represents one of the mechanisms by which the activation of the MD-2/TLR4 ligand LPS promotes DC survival under hypoxic conditions.
The Catalytic Role of RuBisCO for in situ CO2 Recycling in Escherichia coli

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is a key enzyme responsible for biological CO2 assimilation. RuBisCO can be heterologously expressed in Escherichia coli so that glucose and CO2 are co-metabolized to achieve high mixotrophic metabolite production, where the theoretical yield of mixotrophic metabolite production is 2.4 mol(ethanol+acetate+pyruvate)/molglucose. However, RuBisCO is known for its low kcat and for forming inhibited complexes with its substrate ribulose-1,5-bisphosphate (RuBP) and other sugar phosphates, yet the inhibited form of RuBisCO can be reversed by RuBisCO activase (Rca). In this study, RuBisCO forms I and II were cloned and expressed in Escherichia coli for in situ CO2 recycling, where CO2 produced during glucose fermentation was recycled and co-metabolized with the glucose. In addition, forms I and II RuBisCO activases were co-expressed with RuBisCO in E. coli to determine their in vivo effects on in situ CO2 recycling. Form I RuBisCO activase (Rca1) was co-expressed with form I RuBisCO and form II RuBisCO activase (Rca2) was co-expressed with form II RuBisCO. The results showed that both form I and form II RuBisCO exhibit comparable activities in E. coli and generated similar levels of in situ CO2 recycling. A significant increase in the total metabolite yield from 1.5 ± 0.1 to 2.2 ± 0.1 mol(ethanol+acetate+pyruvate)/molglucose occurred when Rca2 was co-expressed with form II RuBisCO. Meanwhile, the total metabolite yield increased from 1.7 ± 0.1 to 2.0 ± 0.1 mol(ethanol+acetate+pyruvate)/molglucose when Rca1 was co-expressed with form I RuBisCO. This data suggests that both forms I and II RuBisCO are subject to in vivo RuBP inhibition yet can be relieved by the co-expression of Rca. Interestingly, it is suggested that the in vivo RuBP inhibition of form II RuBisCO can be more easily reversed compared to form I. When the catalytic power of RuBisCO is maintained by Rca, the high activity of phosphoribulokinase (Prk) plays an important role in directing glucose to the RuBisCO-based engineered pathway and fermentation yields of 2.1–2.3 mol(ethanol+acetate+pyruvate)/molglucose can be obtained. This study is the first to demonstrate that in vivo RuBP inhibition of RuBisCO can be a bottleneck for in situ CO2 recycling in E. coli.
Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro

Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs.
Efficient Body Registration Using Single-View Range Imaging and Generic Shape Templates

Abstract Computer-aided medical systems, e.g. in the fields of medical robotics or image-based assistance, are continuously investigated to overcome human limitations concerning perception, memory or dexterity. A common requirement of such systems is the availability of a digital model describing the patient’s position and morphology during a procedure. Operational complexity and technical limitations of established 3D imaging methods leave clinical settings in need of a method for the fast acquisition of a three-dimensional body surface representation. For this purpose, we propose an unsupervised and efficient body registration pipeline based on the markerless elastic registration and completion of single-view stereo range images of the body surface with statistical parametric body shape templates. Initial results show a promising representative quality of the models generated through the registration process with submillimetric fitting accuracy and realistic surface morphology, indicating the general feasibility of our approach as an instant body registration method for automated medical and biometric applications.