Miracle-dz/UniFAR-FTUs huggingface dataset:
GI inflammation Increases Sodium-Glucose Cotransporter Sglt1

A correlation between gastrointestinal (GI) inflammation and gut hormones has reported that inflammatory stimuli including bacterial endotoxins, lipopolysaccharides (LPS), TNFα, IL-1β, and IL-6 induces high levels of incretin hormone leading to glucose dysregulation. Although incretin hormones are immediately secreted in response to environmental stimuli, such as nutrients, cytokines, and LPS, but studies of glucose-induced incretin secretion in an inflamed state are limited. We hypothesized that GI inflammatory conditions induce over-stimulated incretin secretion via an increase of glucose-sensing receptors. To confirm our hypothesis, we observed the alteration of glucose-induced incretin secretion and glucose-sensing receptors in a GI inflammatory mouse model, and we treated a conditioned media (Mϕ 30%) containing inflammatory cytokines in intestinal epithelium cells and enteroendocrine L-like NCI-H716 cells. In GI-inflamed mice, we observed that over-stimulated incretin secretion and insulin release in response to glucose and sodium glucose cotransporter (Sglt1) was increased. Incubation with Mϕ 30% increases Sglt1 and induces glucose-induced GLP-1 secretion with increasing intracellular calcium influx. Phloridzin, an sglt1 inhibitor, inhibits glucose-induced GLP-1 secretion, ERK activation, and calcium influx. These findings suggest that the abnormalities of incretin secretion leading to metabolic disturbances in GI inflammatory disease by an increase of Sglt1.
Xylopia aethiopica Seeds from Two Countries in West Africa Exhibit Differences in Their Proteomes, Mineral Content and Bioactive Phytochemical Composition

Aside from its multiple medicinal uses, the fruit of Xylopia aethiopica is widely used in Africa as food. Herein, we characterize the protein profiles, mineral content and bioactive phytochemical composition of the seeds of this plant sourced in Ghana and Nigeria. Using label-free proteomics, a total of 677 proteins were identified, with 260 found in the Ghana-sourced samples while 608 proteins were detected in the samples from Nigeria. However, 114 proteins were common between the samples from the two countries, among which 48 were significantly changed. Bioinformatics and functional analyses revealed that the differential levels of the proteins were mainly linked to pathways involved amino acids metabolism and biosynthesis. The significantly changed proteins related mainly to catalytic activity and carbon metabolism. The samples from Nigeria also exhibited superior qualities in terms of their antioxidant effects, and total phenolic and flavonoid content. Finally, only the content of Na varied to a statistically significant level. This study lends support to its culinary use and hints towards the impact of location of cultivation on the quality of the seeds. There is however need for further mechanistic investigations to unravel the underlying reasons for the observed differences.
Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice.

Administration of active growth differentiation factor 11 (GDF11) to aged mice can reduce cardiac hypertrophy, and low serum levels of GDF11 measured together with the related protein, myostatin (also known as GDF8), predict future morbidity and mortality in coronary heart patients. Using mice with a loxP-flanked ("floxed") allele of Gdf11 and Myh6-driven expression of Cre recombinase to delete Gdf11 in cardiomyocytes, we tested the hypothesis that cardiac-specific Gdf11 deficiency might lead to cardiac hypertrophy in young adulthood. We observed that targeted deletion of Gdf11 in cardiomyocytes does not cause cardiac hypertrophy but rather leads to left ventricular dilation when compared to control mice carrying only the Myh6-cre or Gdf11-floxed alleles, suggesting a possible etiology for dilated cardiomyopathy. However, the mechanism underlying this finding remains unclear due to multiple confounding effects associated with the selected model. First, whole heart Gdf11 expression did not decrease in Myh6-cre;Gdf11-floxed mice, possibly due to upregulation of Gdf11 in non-cardiomyocytes in the heart. Second, we observed Cre-associated toxicity, with lower body weights and increased global fibrosis in Cre-only control male mice compared to flox-only controls, making it challenging to infer which changes in Myh6-cre;Gdf11-floxed mice were due to Cre toxicity versus deletion of Gdf11. Third, we observed differential expression of cre mRNA in Cre-only controls compared to the cardiomyocyte-specific knockout mice, also making comparison between these two groups difficult. Thus, targeted Gdf11 deletion in cardiomyocytes may lead to left ventricular dilation without hypertrophy, but alternative animal models are necessary to understand the mechanism for these findings.
Is Sertraline a Good Pharmacological Strategy to Control Anger? Results of a Systematic Review

Introduction: Extensive research has made it possible to conclude that dysfunctions in serotoninergic transmission are associated with a tendency toward violence and behavioral dysregulations in humans. In this regard, it has been suggested that selective serotonin reuptake inhibitors (SSRIs), such as sertraline, which regulate the serotonin system, might reduce proneness to violence. Aims: This review aims to explore changes in feelings of anger-state (e.g., irritability and hostility) and anger expression as primary outcomes after sertraline treatment. Methods: Based on PRISMA quality criteria for reviews, a literature search was carried out through PubMed, PsycINFO, Dialnet, Psicodoc, Web of Knowledge, and the Cochrane Library. Results: Initially, 605 publications were identified, removing 219 duplicate manuscripts and screening the titles and abstracts of the remaining 386 records. This process left 248 articles for full-text reading, finally including 15 entries. Thus, several empirical studies were included that employed different research designs. In this regard, we considered 3 case reports, 5 open clinical trials, and 7 randomized placebo-controlled trials. The majority of the studies were unanimous in concluding that a large percentage of patients with high irritability levels responded satisfactorily to sertraline treatment. In fact, their mood improved, and they experienced a reduction in irritability and anger expression after a few weeks of treatment (approximately two weeks). However, it was necessary to increase the sertraline dose after months of treatment to avoid exhaustion effects. Moreover, not all the patients responded to the treatment and it is particularly interesting that a small percentage of patients were refractory to treatment or even showed an increase in irritability after a few weeks of treatment. In those cases, it was necessary to discontinue the treatment or reduce the dose to the initial levels. Discussion: Although it is necessary to be cautious about the benefits of sertraline as a way to control anger and irritability, it is relevant to consider pharmacological strategies to reduce anger-state as coadjutant treatments to psychotherapy in order to promote lasting changes in violent populations.
Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction.

PURPOSE To establish a sensitive assay for the specific detection of carcinoembryonic antigen (CEA)-expressing tumor cells in the bone marrow of patients with colorectal cancer and other CEA-positive carcinomas. PATIENTS AND METHODS A CEA-specific nested reverse transcriptase (RT) polymerase chain reaction (PCR) assay was developed and optimized using limiting dilutions of a CEA-positive cancer cell line mixed with normal bone marrow cell specimens. The optimized test was then used to examine bone marrow samples obtained from 15 patients with abdominal carcinomas (colorectal, n = 10; pancreatic, n = 3; gastric, n = 2) and six patients with breast cancer. Specificity was assessed by examination of 56 negative controls (malignant hematologic disease, n = 28; nonmalignant disease conditions, n = 5; healthy bone marrow donors, n = 8; normal peripheral-blood samples, n = 15). For 11 patients with abdominal carcinomas, immunostaining evaluations were performed using an anti-CEA and an anticytokeratin antibody, and the results compared with the nested PCR assay. RESULTS In the sensitivity calibration system, single CEA-expressing tumor cells were detected in 2 to 5 x 10(7) normal bone marrow cells. All 56 control samples failed to amplify. This demonstrates that mRNAs coding for highly homologous CEA-related antigens expressed by various lineages of blood cells do not interfere. Bone marrow samples from 10 of 15 patients with abdominal cancers and four of six breast cancer patients scored positive, indicating micrometastatic bone disease. Four of 11 samples from the gastrointestinal cancer patients were found to be positive by the PCR method, but were negative with the immunocytology method. CONCLUSION Since approximately 30% of the colorectal carcinoma patients that score negative in immunocytology staining of bone marrow samples have been reported to relapse, earlier diagnosis of the presence of malignant cells is needed. Our result that samples scoring positive in the described CEA-specific PCR test remained negative by two immunostaining methods suggests a higher sensitivity. We conclude that PCR amplification of CEA mRNA may lead to an earlier diagnosis of micrometastatic bone disease in patients with CEA-expressing carcinomas.
A Mixture Language Model for Class-Attribute Mining from Biomedical Literature Digital Library

We define and study a novel text mining problem for biomedical literature digital library, referred to as the class-attribute mining. Given a collection of biomedical literature from a digital library addressing a set of objects (e.g., proteins) and their descriptions (e.g., protein functions), the tasks of class-attribute mining include: (1) to identify and summarize latent classes in the space of objects, (2) to discover latent attribute themes in the space of object descriptions, and (3) to summarize the commonalities and differences among identified classes along each attribute theme. We approach this mining problem through a mixture language model and estimate the parameters of the model using the EM algorithm. We demonstrate the effectiveness of the model with an application called protein community identification and annotation from Medline, the largest biomedical literature digital library with more than 16 millions abstracts.
Functional MRI and EEG Index Complementary Attentional Modulations

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are two noninvasive methods commonly used to study neural mechanisms supporting visual attention in humans. Studies using these tools, which have complementary spatial and temporal resolutions, implicitly assume they index similar underlying neural modulations related to external stimulus and internal attentional manipulations. Accordingly, they are often used interchangeably for constraining understanding about the impact of bottom-up and top-down factors on neural modulations. To test this core assumption, we simultaneously manipulated bottom-up sensory inputs by varying stimulus contrast and top-down cognitive modulations by changing the focus of spatial attention. Each of the male and female subjects participated in both fMRI and EEG sessions performing the same experimental paradigm. We found categorically different patterns of attentional modulation on fMRI activity in early visual cortex and early stimulus-evoked potentials measured via EEG (e.g., the P1 component and steady-state visually-evoked potentials): fMRI activation scaled additively with attention, whereas evoked EEG components scaled multiplicatively with attention. However, across longer time scales, a contralateral negative-going potential and oscillatory EEG signals in the alpha band revealed additive attentional modulation patterns like those observed with fMRI. These results challenge prior assumptions that fMRI and early stimulus-evoked potentials measured with EEG can be interchangeably used to index the same neural mechanisms of attentional modulations at different spatiotemporal scales. Instead, fMRI measures of attentional modulations are more closely linked with later EEG components and alpha-band oscillations. Considered together, hemodynamic and electrophysiological signals can jointly constrain understanding of the neural mechanisms supporting cognition. SIGNIFICANCE STATEMENT fMRI and EEG have been used as tools to measure the location and timing of attentional modulations in visual cortex and are often used interchangeably for constraining computational models under the assumption that they index similar underlying neural processes. However, by varying attentional and stimulus parameters, we found differential patterns of attentional modulations of fMRI activity in early visual cortex and commonly used stimulus-evoked potentials measured via EEG. Instead, across longer time scales, a contralateral negative-going potential and EEG oscillations in the alpha band exhibited attentional modulations similar to those observed with fMRI. Together, these results suggest that different physiological processes assayed by these complementary techniques must be jointly considered when making inferences about the neural underpinnings of cognitive operations.
Effects of Abscisic Acid and Salicylic Acid on Gene Expression in the Antiviral RNA Silencing Pathway in Arabidopsis

The RNA silencing pathways modulate responses to certain stresses, and can be partially tuned by several hormones such as salicylic acid (SA) and abscisic acid (ABA). Although SA and ABA are often antagonistic and often modulate different stress responses, they have similar effects on virus resistance, which are partially achieved through the antiviral RNA silencing pathway. Whether they play similar roles in regulating the RNA silencing pathway is unclear. By employing coexpression and promoter analyses, we found that some ABA- and SA-related transcription factors (TFs) are coexpressed with several AGO, DCL, and RDR genes, and have multiple binding sites for the identified TFs in the queried promoters. ABA and SA are antagonistic with respect to the expression of AGO1 and RDRs because ABA was able to induce these genes only in the SA mutant. Nevertheless, both hormones showed similarities in the regulation of other genes, for example, the induction of AGO2 by ABA was SA-dependent, indicating that ABA acts upstream of SA in this regulation. We inferred that the similar effects of ABA and SA on some genes resulted in the redundancy of their roles in resistance to bamboo mosaic virus, but that the two hormones are antagonistic with respect to other genes unrelated to their biosynthesis pathways.
Recruiting to a Randomized Controlled Trial of a Web-Based Program for People With Type 2 Diabetes and Depression: Lessons Learned at the Intersection of e-Mental Health and Primary Care

Background E-mental health (eMH) interventions are now widely available and they have the potential to revolutionize the way that health care is delivered. As most health care is currently delivered by primary care, there is enormous potential for eMH interventions to support, or in some cases substitute, services currently delivered face to face in the community setting. However, randomized trials of eMH interventions have tended to recruit participants using online recruitment methods. Consequently, it is difficult to know whether participants who are recruited online differ from those who attend primary care. Objective This paper aimed to document the experience of recruiting to an eMH trial through primary care and compare the characteristics of participants recruited through this and other recruitment methods. Methods Recruitment to the SpringboarD randomized controlled trial was initially focused on general practices in 2 states of Australia. Over 15 months, we employed a comprehensive approach to engaging practice staff and supporting them to recruit patients, including face-to-face site visits, regular contact via telephone and trial newsletters, and development of a Web-based patient registration portal. Nevertheless, it became apparent that these efforts would not yield the required sample size, and we therefore supplemented recruitment through national online advertising and promoted the study through existing networks. Baseline characteristics of participants recruited to the trial through general practice, online, or other sources were compared using the analysis of variance and chi square tests. Results Between November 2015 and October 2017, 780 people enrolled in SpringboarD, of whom 740 provided information on the recruitment source. Of these, only 24 were recruited through general practice, whereas 520 were recruited online and 196 through existing networks. Key barriers to general practice recruitment included perceived mismatch between trial design and diabetes population, prioritization of acute health issues, and disruptions posed by events at the practice and community level. Participants recruited through the 3 different approaches differed in age, gender, employment status, depressive symptoms, and diabetes distress, with online participants being distinguished from those recruited through general practice or other sources. However, most differences reached only a small effect size and are unlikely to be of clinical importance. Conclusions Time, labor, and cost-intensive efforts did not translate into successful recruitment through general practice in this instance, with barriers identified at several different levels. Online recruitment yielded more participants, who were broadly similar to those recruited via general practice.
Aloe emodin exerts potent anticancer effects in MIAPaCa-2 and PANC-1 human pancreatic adenocarcinoma cell lines through activation of both apoptotic and autophagic pathways, sub-G1 cell cycle arrest and disruption of mitochondrial membrane potential (ΛΨm).

PURPOSE To study the anticancer effects of aloe emodin against the MIAPaCa-2 and PANC-1 human pancreatic adenocarcinoma cancer cell lines by evaluating its effect on autophagic cell death, mitochondrial membrane potential (ΛΨm) loss and cell cycle arrest. METHODS The MTT assay was employed to examine the anti-proliferative effect of aloe emodin on these cells, and inverted phase contrast and fluorescence microscopes were used to evaluate apoptotic induction. Flow cytometry was performed to examine the effects of aloe emodin on ΛΨm and cell cycle phase distribution. RESULTS The findings indicated that aloe emodin induced dose-dependent cytotoxicity in both pancreatic carcinoma cells with MIAPaCa-2 cells being more susceptible than PANC-1, along with inhibiting cancer cell colony formation. Aloe emodin-treated cells exhibited cell shrinkage along with distortion of the normal cell morphology. In addition, these cells showed chromatin condensation, membrane blebbing and predominantly emitted red fluorescence, which signified apoptosis. Following treatment with aloe emodin (10, 40 and 80 µM) the early apoptotic cell percentage increased to 17.5, 39.6 and 58.8%, respectively, while late apoptotic cells percentage increased to 22.3, 27.6 and 37.2% respectively. There was also a marked increase in the loss of ΛΨm in the aloe emodin-treated cells, as well as dose-dependent sub-G1 cell cycle arrest. Furthermore, aloe emodin treatment led to a substantial enhancement of the conversion of light chain 3 (LC3)-l to LC3-ll and this increase was shown to follow aloe emodin dose-dependent pattern, thus indicating that aloe emodin may induce autophagy in addition to apoptosis. CONCLUSION To sum up, aloe emodin inhibits cancer cell growth in human pancreatic carcinoma cells and it was shown that these anticancer effects are mediated via both apoptotic and autophagic pathways, cell cycle arrest and loss of mitochondrial membrane potential.
Derivation of novel naive‐like porcine embryonic stem cells by a reprogramming factor‐assisted strategy

The establishment of ungulate embryonic stem cells (ESCs) has been notoriously difficult via a conventional approach. We combined a traditional ESC culture method with reprogramming factors to assist the establishment of porcine naive‐like ESCs (nESCs). Pig embryonic fibroblasts were transfected with a tetracycline‐inducible vector carrying 4 classic mouse reprogramming factors, followed by somatic cell nuclear transfer and culturing to the blastocyst stage. Then, the inner cell mass was isolated and seeded in culture medium. The naive‐like ESCs had characteristic verys similar to those of mouse ESCs and showed no signs of altered morphology or differentiation, even after 130 passages. They depended on leukemia inhibitory factor signals for maintenance of pluripotency, and the female cell lines had low expression of the X‐inactive specific transcript gene and no histone H3 lysine 27 trimethylation spot. Notably, the ESCs differentiated into 3 germ layers in vitro and could be induced to undergo directional neural and kidney precursor differentiation under defined conditions, and the ESCs could keep proliferating after doxycycline was removed. nESCs can be established, and the well‐characterized ESC lines will be useful for the research of transgenic pig models for human disease. —Zhang, M. , Wang, C. , Jiang, H. , Liu, M. , Yang, N. , Zhao, L. , Hou, D. , Jin, Y. , Chen, Q. , Chen, Y. , Wang, J., Dai, Y. , Li, R. Derivation of novel naive‐like porcine embryonic stem cells by a reprogramming factor–assisted strategy. FASEB J. 33, 9350–9361 (2019). www.fasebj. org
Effects of Organic and Conventional Growing Systems on the Phenolic Profile of Extra-Virgin Olive Oil

Extra-virgin olive oil (EVOO) is largely appreciated for its proven nutritional properties. Additionally, organic foods are perceived as healthier by consumers. In this context, the aim of the present study was to compare the phenolic profiles of EVOO from olives of the Hojiblanca variety, cultivated under organic and conventional systems. The quantification and identification of individual polyphenols was carried out by liquid chromatography coupled to mass spectrometry in tandem mode (LC-MS/MS). Significantly higher levels (p < 0.05) of phenolic compounds were found in organic EVOOs. The methodology used was able to detect previously unreported differences in bioactive components between organic and conventional EVOOs.
What is the Long-Term Follow-Up of Nonoperatively Treated Patients with Appendicitis?

In this study, we determine outcomes after nonoperative treatment of appendicitis. First, we abstracted data for patients discharged with a diagnosis of appendicitis from a tertiary care facility from August 1, 2007, through June 30, 2017. For patients treated nonoperatively, we collected additional medical treatment for appendicitis, future surgical treatment, and date of last follow-up. In our study, we identified 487 patients treated for appendicitis. From this group, 66 patients were successfully treated nonoperatively. Eight patients (12%) had an interval appendectomy at a mean follow-up time of two months. Of the 58 remaining patients, 20 (34%) did not have any further appendicitis-related issues over a mean follow-up period of 25 months. A total of 38 (66%) had recurring or additional concerns requiring further treatment or emergent surgery within a mean time of four months. A large proportion, 76 per cent (n = 29), required unscheduled or emergent appendectomy. There were more patients diagnosed with an abscess (55%) in the group that had further appendicitis issues. In conclusion, nonoperative treatment of appendicitis is associated with significant likelihood of future appendicitis-related treatment or emergency surgery (66%). In addition, patients diagnosed with an abscess are at particularly high risk of future appendicitis-related issues.