Miracle-dz/UniFAR-FTUs huggingface dataset:
Untargeted Metabolic Profiling Cell-Based Approach of Pulmonary Artery Smooth Muscle Cells in Response to High Glucose and the Effect of the Antioxidant Vitamins D and E

Pulmonary arterial hypertension (PAH) is a multi-factorial disease characterized by the hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Excessive reactive oxygen species (ROS) formation resulted in alterations of the structure and function of pulmonary arterial walls, leading to right ventricular failure and death. Diabetes mellitus has not yet been implicated in pulmonary hypertension. However, recently, variable studies have shown that diabetes is correlated with pulmonary hypertension pathobiology, which could participate in the modification of pulmonary artery muscles. The metabolomic changes in PASMCs were studied in response to 25 mM of D-glucose (high glucose, or HG) in order to establish a diabetic-like condition in an in vitro setting, and compared to five mM of D-glucose (normal glucose, or LG). The effect of co-culturing these cells with an ideal blood serum concentration of cholecalciferol-D3 and tocopherol was also examined. The current study aimed to examine the role of hyperglycemia in pulmonary arterial hypertension by the quantification and detection of the metabolomic alteration of smooth muscle cells in high-glucose conditions. Untargeted metabolomics was carried out using hydrophilic interaction liquid chromatography and high-resolution mass spectrometry. Cell proliferation was assessed by cell viability and the [3H] thymidine incorporation assay, and the redox state within the cells was examined by measuring reactive oxygen species (ROS) generation. The results demonstrated that PASMCs in high glucose (HG) grew, proliferated faster, and generated higher levels of superoxide anion (O2·−) and hydrogen peroxide (H2O2). The metabolomics of cells cultured in HG showed that the carbohydrate pathway, especially that of the upper glycolytic pathway metabolites, was influenced by the activation of the oxidation pathway: the pentose phosphate pathway (PPP). The amount of amino acids such as aspartate and glutathione reduced via HG, while glutathione disulfide, N6-Acetyl-L-lysine, glutamate, and 5-aminopentanoate increased. Lipids either as fatty acids or glycerophospholipids were downregulated in most of the metabolites, with the exception of docosatetraenoic acid and PG (16:0/16:1(9Z)). Purine and pyrimidine were influenced by hyperglycaemia following PPP oxidation. The results in addition showed that cells exposed to 25 mM of glucose were oxidatively stressed comparing to those cultured in five mM of glucose. Cholecalciferol (D3, or vitamin D) and tocopherol (vitamin E) were shown to restore the redox status of many metabolic pathways.
A qualitative exploration of menstruation-related restrictive practices in Fiji, Solomon Islands and Papua New Guinea

Attitudes and beliefs about menstruation can place restrictions on menstruating women and girls, limiting their ability to fully participate in community life, education and employment. This paper presents evidence on menstruation-related beliefs contributing to restrictive practices in Papua New Guinea (PNG), Solomon Islands (SI) and Fiji. Focus group discussions and interviews were undertaken with 307 adolescent girls, women and men in a rural and urban site in each country. Data were analysed using an inductive thematic approach. Participants described a range of attitudes and beliefs that restrict the behaviour of menstruating women and girls. Themes include the belief that menstrual blood is ‘dirty’; that when menstruating, girls and women can bring ‘bad luck’ to men; secrecy and shame associated with menstruation; and beliefs about the impact of certain behaviours on menstruation and health. Restrictive practices were more frequently reported in PNG and SI than Fiji, and more common in rural compared with urban sites. Some restrictions, such as avoidance of household chores, were perceived as desirable or driven by women themselves. However participants identified other restrictions, such as not being able to attend church or hygienically wash menstrual hygiene materials, as unwanted, in some cases impacting on participation in school, work and community life. Education initiatives guided by women and girls, implemented by local stakeholders and grounded in a sound understanding of specific contexts are needed to address discriminatory attitudes and beliefs that contribute to unwanted restrictions, and to support enabling attitudes and beliefs regarding menstruation.
ERBB2 mutation frequency in lobular breast cancer with pleomorphic histology or high‐risk characteristics by molecular expression profiling

HER2‐positive breast cancer is defined by amplification or overexpression of the HER2/ERBB2 oncogene and accounts for about 15% of breast cancer cases. Somatic mutation of ERBB2 is an alternative mechanism, by which activation of HER2 signaling can occur. ERBB2 mutation has been associated with invasive lobular breast cancer (ILBC). This study investigates the frequency and phenotype of ILBC harboring mutated ERBB2. The ERBB2 mutation status was determined by next generation sequencing and/or pyrosequencing in n = 106 ILBCs, including n = 86 primary or locally recurrent tumors and n = 20 metastases from visceral organs, soft tissue, or skin. Immunohistochemical characteristics were determined using tissue microarrays. This series was enriched for ILBCs with pleomorphic histology and/or high‐risk expression profiles (Oncotype DX, recurrence score RS > 25). Nearly all specimens were E‐cadherin‐negative (99%), estrogen receptor (ER)‐positive (92%), and lacked ERBB2 overexpression (96%). ERBB2 mutations (p.V777L, p.L755S, p.S310F) were identified in 5/106 (5%) cases. ERBB2‐mutated cases included 2/86 (2%) primary tumors and 3/20 (15%) metastases (P = 0.045). ERBB2‐mutated cases were associated with loss of ER (2/7, 29%, P = 0.035) and histological grade 3 (4/34, 12%, P = 0.023), but not with solid growth (3/31, 10%, P = 0.148) or pleomorphic histology (2/27, 7%, P = 0.599). No ERBB2 mutation was detected in ILBCs with RS > 25 (0/22, 0%). In 10 patients with multiple matched specimens (n = 25), the ERBB2 mutational status was always concordant. In summary, a small subset of ILBCs harbors potentially actionable ERBB2 mutations. In ERBB2‐mutated ILBCs, no association with pleomorphic histology was found.
Reducing Social Judgment Biases May Require Identifying the Potential Source of Bias

Social judgment is shaped by multiple biases operating simultaneously, but most bias-reduction interventions target only a single social category. In seven preregistered studies (total N > 7,000), we investigated whether asking participants to avoid one social bias affected that and other social biases. Participants selected honor society applicants based on academic credentials. Applicants also differed on social categories irrelevant for selection: attractiveness and ingroup status. Participants asked to avoid potential bias in one social category showed small but reliable reductions in bias for that category (r = .095), but showed near-zero bias reduction on the unmentioned social category (r = .006). Asking participants to avoid many possible social biases or alerting them to bias without specifically identifying a category did not consistently reduce bias. The effectiveness of interventions for reducing social biases may be highly specific, perhaps even contingent on explicitly and narrowly identifying the potential source of bias.
How to Make the Best Use of Intraoperative Motor Evoked Potential Monitoring? Experience in 1162 Consecutive Spinal Deformity Surgical Procedures

Study Design. A retrospective study of 1162 consecutive patients who underwent spinal deformity surgical procedures at our spine center from January 2010 to December 2013. Objective. To develop and evaluate a protocol of intraoperative motor evoked potential (MEP) monitoring with the warning criteria we had established on the basis of our clinical experiences and the review of previous literature. Summary of Background Data. Though MEPs monitoring have become widely used in spinal deformity surgery, different alarm criteria and response protocol used in different studies compromised their comparability; Furthermore, high false-positive rate of MEP reported by previous studies has become an increasingly prominent problem that will limit its clinical use and development. Methods. The intraoperative monitoring data of 1162 consecutive patients who underwent spinal deformity surgical procedures at our spine center were retrospectively analyzed. Age, sex, diagnosis, preoperative neurological status, intraspinal anomalies, baseline MEP, and MEP change were collected. The protocol with the warning criteria we had established was used. The false-positive rate, false-negative rate, and positive predictive value were calculated. Results. Significant intraoperative changes were seen in the MEP data in 52 (4.4%) of all the cases. In 25 cases among which, significant MEP changes were synchronously and logically associated with high-risk surgical maneuver (pedicle screw insertion, osteotomy, correction, etc.). The false-positive rate of MEP monitoring was 0.26% (3/1140), whereas the sensitivity and specificity of MEP for detection of clinically significant intraoperative cord injury were 100% and 99.7%, respectively. The positive predictive value of a MEP alert in terms of a new postoperative neurological deficit was 83.3%. Conclusion. Our study indicates that the appropriate use of MEP monitoring based on our protocol is able to obtain satisfying sensitivity and specificity and thus provide important information for intraoperative decision making. Level of Evidence: 4
Regulatory role of vitamin E in the immune system and inflammation

Vitamin E, a potent lipid‐soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients known to modulate immune function. Vitamin E deficiency has been demonstrated to impair normal functions of the immune system in animals and humans, which can be corrected by vitamin E repletion. Although deficiency is rare, vitamin E supplementation above current dietary recommendations has been shown to enhance the function of the immune system and reduce risk of infection, particularly in older individuals. The mechanisms responsible for the effect of vitamin E on the immune system and inflammation have been explored in cell‐based, pre‐clinical and clinical intervention studies. Vitamin E modulates T cell function through directly impacting T cell membrane integrity, signal transduction, and cell division, and also indirectly by affecting inflammatory mediators generated from other immune cells. Modulation of immune function by vitamin E has clinical relevance as it affects host susceptibility to infectious diseases such as respiratory infections, in addition to allergic diseases such as asthma. Studies examining the role of vitamin E in the immune system have typically focused on α‐tocopherol; however, emerging evidence suggests that other forms of vitamin E, including other tocopherols as well as tocotrienols, may also have potent immunomodulatory functions. Future research should continue to identify and confirm the optimal doses for individuals at different life stage, health condition, nutritional status, and genetic heterogeneity. Future research should also characterize the effects of non‐α‐alpha‐tocopherol vitamin E on immune cell function as well as their potential clinical application. © 2018 IUBMB Life, 71(4):487–494, 2019
The Role of Omega-3 Fatty Acids in the Setting of Coronary Artery Disease and COPD: A Review

Chronic obstructive pulmonary disease (COPD) is a growing healthcare concern and will represent the third leading cause of death worldwide within the next decade. COPD is the result of a complex interaction between environmental factors, especially cigarette smoking, air pollution, and genetic preconditions, which result in persistent inflammation of the airways. There is growing evidence that the chronic inflammatory state, measurable by increased levels of circulating cytokines, chemokines, and acute phase proteins, may not be confined to the lungs. Cardiovascular disease (CVD) and especially coronary artery disease (CAD) are common comorbidities of COPD, and low-grade systemic inflammation plays a decisive role in its pathogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert multiple functions in humans and are crucially involved in limiting and resolving inflammatory processes. n-3 PUFAs have been intensively studied for their ability to improve morbidity and mortality in patients with CVD and CAD. This review aims to summarize the current knowledge on the effects of n-3 PUFA on inflammation and its impact on CAD in COPD from a clinical perspective.
Mammography and ultrasound effective features in differentiating basal-like and normal-like subtypes of triple negative breast cancer

The aim of our study was to find effective features of mammography and ultrasound in differentiating Basal-like breast cancer (BBC) and Normal-like breast cancer (NBC), two subtypes of triple negative breast cancer (TNBC). From January 2014 to March 2017, we retrospectively reviewed 91 patients who were pathologically confirmed as TNBC. According to immunohistochemical cytokeratin 5/6 (CK5/6) and Epidermal Growth Factor Receptor (EGFR), TNBCs were classified into BBCs group and NBCs group. Both CK5/6 and EGFR were negative defined to be NBC, whereas if any of CK5/6 or EGFR was positive then defined as BBC. BBCs group concluded 65 (71.4%) cases and NBCs group concluded26 (28.6%) cases. Ultrasound images and mammograms were reevaluated by breast imaging experts according to the breast imaging reporting and data system (BI-RADS) 4th edition. On mammography, masses margins had significant differences between BBCs group and NBCs group (P = 0.024). Most BBCs margins exhibited microlobulated (30/64, 46.9%) or spiculated (25/64, 39.0%), whereas most NBCs margins exhibited microlobulated (17/23, 73.9%). On ultrasound, BBCs were more frequently to present as larger than 20mm lesions (52/65, 80.0%) and more likely to have angular or spiculated margins (35/65, 53.8%), additionally, compared with NBCs, BBCs were less likely to have calcification (1/65, 1.5%). Other mammography and ultrasound features showed no significant differences between the two groups. In conclusion, we have found some effective features of mammography and ultrasound that could be helpful in differentiating BBC and NBC, which will provide some useful references for clinical diagnosis and treatment.
The evolving role of receptors as predictive biomarkers for metastatic breast cancer

ABSTRACT Introduction: In breast cancer, estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are essential biomarkers to predict response to endocrine and anti-HER2 therapies, respectively. In metastatic breast cancer, the use of these receptors and targeted therapies present additional challenges: temporal heterogeneity, together with limited sampling methodologies, hinders receptor status assessment, and the constant evolution of the disease invariably leads to resistance to treatment. Areas covered: This review summarizes the genomic abnormalities in ER and HER2, such as mutations, amplifications, translocations, and alternative splicing, emerging as novel biomarkers that provide an insight into underlying mechanisms of resistance and hold potential predictive value to inform treatment selection. We also describe how liquid biopsies for sampling of circulating markers and ultrasensitive detection technologies have emerged which complement ongoing efforts for biomarker discovery and analysis. Expert commentary: While evidence suggests that genomic aberrations in ER and HER2 could contribute to meeting the pressing need for better predictive biomarkers, efforts need to be made to standardize assessment methods and better understand the resistance mechanisms these markers denote. Taking advantage of emerging technologies, research in upcoming years should include prospective trials incorporating these predictors into the study design to validate their potential clinical value.
Datura and Brugmansia plants related antimuscarinic toxicity: an analysis of poisoning cases reported to the Taiwan poison control center

Abstract Introduction: Datura and Brugmansia plants, especially Datura species, have been used for their hallucinogenic effects in the United States and Europe; whereas Datura plants have been used as a traditional medicine in many Asian countries. This study was conducted to better understand the pattern and outcome of Datura/Brugmansia plant related poisoning in Taiwan. Methods: This is a retrospective case series study of all cases with Datura/Brugmansia exposure reported to the Taiwan Poison Control Center between 1986 and 2015. Data for patients with relevant poisoning were reviewed and abstracted. Logistic regression analysis was used to identify potential predictors of the severity of poisoning; bivariate analysis was employed to assess the effectiveness of physostigmine in the treatment of Datura/Brugmansia poisoning. Results: A total of 203 cases involving 114 Datura exposures and 89 Brugmansia suaveolens exposures were eligible for analysis. Using Datura/Brugmansia for a medicinal purpose by the patients without consulting Chinese medicine practitioners was the most common reason of poisoning (81.2%); whereas only 2% of the patients were poisoned after medicinal use associated with the prescription from Chinese medicine practitioners. None of the 203 patients had used Datura/Brugmansia plant for recreational purpose. Most frequently observed clinical effect was mydriasis (53.2%), followed by confusion (40%), tachycardia (35.5%), dry mouth (35.5%), dizziness (34%), dry skin (32.5%), and delirium (31%). Seventy-three cases (36%) had severe effects; none of them died. Misidentification of the plants and ingestion of plant parts other than flowers were positively associated with the severity of poisoning. Forty patients (19.7%) received physostigmine therapy and patients receiving physostigmine had an earlier resolution of central nervous system toxicity than those who did not. Conclusions: Medicinal use without consulting Chinese medicine practitioners is the main reason for Datura/Brugmansia poisoning in Taiwan. Consumption of parts other than flowers and misidentification of the plants predicted the severity of poisoning in this study. Patients who received physostigmine appear to have earlier improvement in the central nervous system effects. No adverse events were reported from physostigmine administration.
Face-Focused Cross-Stream Network for Deception Detection in Videos

Automated deception detection (ADD) from real-life videos is a challenging task. It specifically needs to address two problems: (1) Both face and body contain useful cues regarding whether a subject is deceptive. How to effectively fuse the two is thus key to the effectiveness of an ADD model. (2) Real-life deceptive samples are hard to collect; learning with limited training data thus challenges most deep learning based ADD models. In this work, both problems are addressed. Specifically, for face-body multimodal learning, a novel face-focused cross-stream network (FFCSN) is proposed. It differs significantly from the popular two-stream networks in that: (a) face detection is added into the spatial stream to capture the facial expressions explicitly, and (b) correlation learning is performed across the spatial and temporal streams for joint deep feature learning across both face and body. To address the training data scarcity problem, our FFCSN model is trained with both meta learning and adversarial learning. Extensive experiments show that our FFCSN model achieves state-of-the-art results. Further, the proposed FFCSN model as well as its robust training strategy are shown to be generally applicable to other human-centric video analysis tasks such as emotion recognition from user-generated videos.
Reduction of Cardiovascular Risk and Improved Estimated Glomerular Filtration Rate by SGLT2 Inhibitors, Including Dapagliflozin, Is Consistent Across the Class: An Analysis of the Placebo Arm of EXSCEL

OBJECTIVE The sodium–glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin and canagliflozin reduce the incidence of major adverse cardiovascular events (MACE), all-cause mortality (ACM), and renal events in cardiovascular outcomes trials, with observational real-world evidence suggesting class effect benefits that include dapagliflozin. We examined the placebo arm of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) to determine whether the effects of drop-in open-label dapagliflozin on MACE, ACM, and estimated glomerular filtration rate (eGFR) were consistent with the SGLT2i class as a whole. RESEARCH DESIGN AND METHODS SGLT2i drop-in therapy occurred in 10.6% of EXSCEL participants, with 5.2% taking dapagliflozin. Propensity-matched cohorts of SGLT2i users and nonusers (n = 709 per group) were generated on the basis of their characteristics before open-label SGLT2i drop-in or at baseline for participants taking SGLT2i at enrollment and an equivalent study visit for non-SGLT2i users. Time to first adjudicated MACE and ACM was analyzed using Cox regression. eGFR slopes were compared between matched cohorts using a mixed-model repeated-measures analysis. RESULTS In adjusted analyses, SGLT2i users (compared with nonusers) had a numerically lower risk of MACE (adjusted hazard ratio 0.79 [95% CI 0.49–1.28]), as did dapagliflozin users (0.55 [0.26–1.15]). SGLT2i users had a significantly lower ACM risk (0.51 [0.27–0.95]; dapagliflozin: 0.66 [0.25–1.72]). Compared with nonusers, eGFR slope was significantly better for SGLT2i users overall (+1.78 [95% CI 0.87–2.69] mL/min/1.73 m2 per year) and for dapagliflozin users (+2.28 [1.01–3.54] mL/min/1.73 m2 per year). CONCLUSIONS This post hoc analysis of the placebo arm of EXSCEL supports a beneficial class effect for all SGLT2i, including dapagliflozin, for reduced ACM and less eGFR decline.
High-Dimensional Entanglement in States with Positive Partial Transposition.

Genuine high-dimensional entanglement, i.e., the property of having a high Schmidt number, constitutes an instrumental resource in quantum communication, overcoming limitations of low-dimensional systems. States with a positive partial transpose (PPT) are generally considered weakly entangled, as they can never be distilled into pure entangled states. This naturally raises the question of whether high Schmidt numbers are possible for PPT states. Volume estimates suggest that optimal, i.e., linear, scaling in the local dimension should be possible, albeit without providing insight into the possible slope. We provide the first explicit construction of a family of PPT states that achieves linear scaling in the local dimension and we prove that random PPT states typically share this feature. Our construction also allows us to prove a recent conjecture of Chen et al. on the existence of PPT states whose Schmidt number increases by an arbitrarily large amount upon partial transposition. Finally, we link the Schmidt number to entangled sub-block matrices of a quantum state. We use this connection to prove that quantum states that are either (i) invariant under partial transposition on the smallest of their two subsystems, or (ii) absolutely PPT cannot have a maximal Schmidt number. Overall, our findings shed new light on some fundamental problems in entanglement theory.