Miracle-dz/UniFAR-FTUs huggingface dataset:
Feature article: LCZ696, an angiotensin receptor-neprilysin inhibitor, ameliorates diabetic cardiomyopathy by inhibiting inflammation, oxidative stress and apoptosis

Diabetic cardiomyopathy, which refers to the destruction of the structure and function of the heart, is the primary cause of heart failure due to diabetes. LCZ696 is the first angiotensin receptor-neprilysin inhibitor (ARNi) to be used clinically. Our study investigated the role played by LCZ696 during diabetic cardiomyopathy and explored the potential mechanisms underlying these effects. Diabetes was induced by injecting streptozotocin intraperitoneally into mice, and the mice were then divided randomly into two groups: one group was treated with LCZ696 (60 mg/kg/d) for 16 weeks, and the other received no treatment. The H9C2 cardiomyoblast cell line was treated with LCZ696 under high-glucose (HG) conditions. The levels of apoptotic (Bax, Bcl-2 and cleaved caspase-3) and pro-inflammatory factors [nuclear factor (NF)-κB, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated kinase (MAPK)] were assessed in heart tissues from diabetic and normal mice and in H9C2 cells. The heart tissue structures and cardiac functions of diabetic mice were compared with those of normal mice, using histological and echocardiographic analyses. The results showed that LCZ696 inhibits the nuclear transfer of NF-κB and JNK/p38MAPK phosphorylation, and mitigates inflammation and apoptosis in diabetic mice and H9C2 cardiomyocytes under HG conditions. The histological and echocardiographic data showed that compared with untreated diabetic mice, diabetic mice treated with LCZ696 exhibited improved ventricular remodeling and cardiac function. LCZ696 also ameliorated oxidative stress in both vivo and vitro. In conclusion, LCZ696 improved diabetic cardiomyopathy by reducing cardiac inflammation, oxidative stress, and apoptosis. Impact statement Diabetic cardiomyopathy (DCM) is an important cause of heart failure in patients with diabetes, resulting in increased morbidity and mortality. LCZ696, which was studied here, is a novel drug for the treatment of heart failure. The latest research reports that LCZ696 is more effective for preventing heart failure than valsartan alone. However, little research has been performed examining the effects of LCZ696 on DCM. This study was designed to examine the role played by LCZ696 during DCM and the potential mechanisms underlying these effects, which may provide the basis for a new therapeutic strategy for DCM.
Internal Carotid Artery Blood Flow Response to Anesthesia, Pneumoperitoneum, and Head-up Tilt during Laparoscopic Cholecystectomy.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC Cardiac output is an independent regulator of cerebral blood flow in healthy awake humansThe relationship between cardiac output and cerebral blood flow in anesthetized patients undergoing laparoscopy has not been previously characterized WHAT THIS ARTICLE TELLS US THAT IS NEW: At steady-state depth of anesthesia, in patients undergoing laparoscopic cholecystectomy, creation of pneumoperitoneum decreased cardiac output and internal carotid artery blood flow while mean arterial pressure and end-tidal carbon dioxide levels remained unchanged BACKGROUND:: Little is known about how implementation of pneumoperitoneum and head-up tilt position contributes to general anesthesia-induced decrease in cerebral blood flow in humans. We investigated this question in patients undergoing laparoscopic cholecystectomy, hypothesizing that cardiorespiratory changes during this procedure would reduce cerebral perfusion. METHODS In a nonrandomized, observational study of 16 patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy, internal carotid artery blood velocity was measured by Doppler ultrasound at four time points: awake, after anesthesia induction, after induction of pneumoperitoneum, and after head-up tilt. Vessel diameter was obtained each time, and internal carotid artery blood flow, the main outcome variable, was calculated. The authors recorded pulse contour estimated mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV) index, cardiac index, end-tidal carbon dioxide (ETCO2), bispectral index, and ventilator settings. Results are medians (95% CI). RESULTS Internal carotid artery blood flow decreased upon anesthesia induction from 350 ml/min (273 to 410) to 213 ml/min (175 to 249; -37%, P < 0.001), and tended to decrease further with pneumoperitoneum (178 ml/min [127 to 208], -15%, P = 0.026). Tilt induced no further change (171 ml/min [134 to 205]). ETCO2 and bispectral index were unchanged after induction. MAP decreased with anesthesia, from 102 (91 to 108) to 72 (65 to 76) mmHg, and then remained unchanged (Pneumoperitoneum: 70 [63 to 75]; Tilt: 74 [66 to 78]). Cardiac index decreased with anesthesia and with pneumoperitoneum (overall from 3.2 [2.7 to 3.5] to 2.3 [1.9 to 2.5] l · min · m); tilt induced no further change (2.1 [1.8 to 2.3]). Multiple regression analysis attributed the fall in internal carotid artery blood flow to reduced cardiac index (both HR and SV index contributing) and MAP (P < 0.001). Vessel diameter also declined (P < 0.01). CONCLUSIONS During laparoscopic cholecystectomy, internal carotid artery blood flow declined with anesthesia and with pneumoperitoneum, in close association with reductions in cardiac index and MAP. Head-up tilt caused no further reduction. Cardiac output independently affects human cerebral blood flow.
A Ligand-Based Virtual Screening Method Using Direct Quantification of Generalization Ability

Machine learning plays an important role in ligand-based virtual screening. However, conventional machine learning approaches tend to be inefficient when dealing with such problems where the data are imbalanced and features describing the chemical characteristic of ligands are high-dimensional. We here describe a machine learning algorithm LBS (local beta screening) for ligand-based virtual screening. The unique characteristic of LBS is that it quantifies the generalization ability of screening directly by a refined loss function, and thus can assess the risk of over-fitting accurately and efficiently for imbalanced and high-dimensional data in ligand-based virtual screening without the help of resampling methods such as cross validation. The robustness of LBS was demonstrated by a simulation study and tests on real datasets, in which LBS outperformed conventional algorithms in terms of screening accuracy and model interpretation. LBS was then used for screening potential activators of HIV-1 integrase multimerization in an independent compound library, and the virtual screening result was experimentally validated. Of the 25 compounds tested, six were proved to be active. The most potent compound in experimental validation showed an EC50 value of 0.71 µM.
4D Printing of Multi-Hydrogels Using Direct Ink Writing in a Supporting Viscous Liquid

We propose a method to print four-dimensional (4D) stimuli-responsive hydrogel structures with internal gaps. Our 4D structures are fabricated by printing an N-isopropylacrylamide-based stimuli-responsive pre-gel solution (NIPAM-based ink) and an acrylamide-based non-responsive pre-gel solution (AAM-based ink) in a supporting viscous liquid (carboxymethyl cellulose solution) and by polymerizing the printed structures using ultraviolet (UV) light irradiation. First, the printed ink position and width were investigated by varying various parameters. The position of the printed ink changed according to physical characteristics of the ink and supporting liquid and printing conditions including the flow rates of the ink and the nozzle diameter, position, and speed. The width of the printed ink was mainly influenced by the ink flow rate and the nozzle speed. Next, we confirmed the polymerization of the printed ink in the supporting viscous liquid, as well as its responsivity to thermal stimulation. The degree of polymerization became smaller, as the interval time was longer after printing. The polymerized ink shrunk or swelled repeatedly according to thermal stimulation. In addition, printing multi-hydrogels was demonstrated by using a nozzle attached to a Y shape connector, and the responsivity of the multi-hydrogels to thermal-stimulation was investigated. The pattern of the multi-hydrogels structure and its responsivity to thermal-stimulation were controlled by the flow ratio of the inks. Finally, various 4D structures including a rounded pattern, a spiral shape pattern, a cross point, and a multi-hydrogel pattern were fabricated, and their deformations in response to the stimuli were demonstrated.
Prognostic Significance of TWIST1, CD24, CD44, and ALDH1 Transcript Quantification in EpCAM-Positive Circulating Tumor Cells from Early Stage Breast Cancer Patients

(1) Background: The aim of the study was to evaluate the prognostic significance of EMT-associated (TWIST1) and stem-cell (SC) transcript (CD24, CD44, ALDH1) quantification in EpCAM+ circulating tumor cells (CTCs) of early breast cancer patients. (2) Methods: 100 early stage breast cancer patients and 19 healthy donors were enrolled in the study. CD24, CD44, and ALDH1 transcripts of EpCAM+ cells were quantified using a novel highly sensitive and specific quadraplex RT-qPCR, while TWIST1 transcripts were quantified by single RT-qPCR. All patients were followed up for more than 5 years. (3) Results: A significant positive correlation between overexpression of TWIST1 and CD24−/low/CD44high profile was found. Kaplan–Meier analysis revealed that the ER/PR-negative (HR-) patients and those patients with more than 3 positive lymph nodes that overexpressed TWIST1 in EpCAM+ cells had a significant lower DFI (log rank test; p < 0.001, p < 0.001) and OS (log rank test; p = 0.006, p < 0.001). Univariate and multivariate analysis also revealed the prognostic value of TWIST1 overexpression and CD24−/low/CD44high and CD24−/low/ALDH1high profile for both DFI and OS. (4) Conclusions: Detection of TWIST1 overexpression and stem-cell (CD24, CD44, ALDH1) transcripts in EpCAM+ CTCs provides prognostic information in early stage breast cancer patients.
Wearable Woven Triboelectric Nanogenerator Utilizing Electrospun PVDF Nanofibers for Mechanical Energy Harvesting

Several wearable devices have already been commercialized and are likely to open up a new life pattern for consumers. However, the limited energy capacity and lifetime have made batteries the bottleneck in wearable technology. Thus, there have been growing efforts in the area of self-powered wearables that harvest ambient mechanical energy directly from surroundings. Herein, we demonstrate a woven triboelectric nanogenerator (WTENG) utilizing electrospun Polyvinylidene fluoride (PVDF) nanofibers and commercial nylon cloth to effectively harvest mechanical energy from human motion. The PVDF nanofibers were fabricated using a highly scalable multi-nozzle far-field centrifugal electrospinning protocol. We have also doped the PVDF nanofibers with small amounts of multi-walled carbon nanotubes (MWCNT) to improve their triboelectric performance by facilitating the growth of crystalline β-phase with a high net dipole moment that results in enhanced surface charge density during contact electrification. The electrical output of the WTENG was characterized under a range of applied forces and frequencies. The WTENG can be triggered by various free-standing triboelectric layers and reaches a high output voltage and current of about 14 V and 0.7 µA, respectively, for the size dimensions 6 × 6 cm. To demonstrate the potential applications and feasibility for harvesting energy from human motion, we have integrated the WTENG into human clothing and as a floor mat (or potential energy generating shoe). The proposed triboelectric nanogenerator (TENG) shows promise for a range of power generation applications and self-powered wearable devices.
The Association Between Physiological Noise Levels and Speech Understanding in Noise

Objectives: Traditionally, elevated hearing thresholds have been considered to be the main contributors to difficulty understanding speech in noise; yet, patients will often report difficulties with speech understanding in noise despite having audiometrically normal hearing. The purpose of this cross-sectional study was to critically evaluate the relationship of various metrics of auditory function (behavioral thresholds and otoacoustic emissions) on speech understanding in noise in a large sample of audiometrically normal-hearing individuals. Design: Behavioral hearing thresholds, distortion product otoacoustic emission (DPOAE) levels, stimulus-frequency otoacoustic emission levels, and physiological noise (quantified using OAE noise floors) were measured from 921 individuals between 10 and 68 years of age with normal pure-tone averages. The quick speech-in-noise (QuickSIN) test outcome, quantified as the signal-to-noise ratio (SNR) loss, was used as the metric of speech understanding in noise. Principle component analysis (PCA) and linear regression modeling were used to evaluate the relationship between the measures of auditory function and speech in noise performance. Results: Over 25% of participants exhibited mild or worse degree of SNR loss. PCA revealed DPOAE levels at 12.5 to 16 kHz to be significantly correlated with the variation in QuickSIN scores, although correlations were weak (R2 = 0.017). Out of all the metrics evaluated, higher levels of self-generated physiological noise accounted for the most variance in QuickSIN performance (R2 = 0.077). Conclusions: Higher levels of physiological noise were associated with worse QuickSIN performance in listeners with normal hearing sensitivity. We propose that elevated physiological noise levels in poorer speech in noise performers could diminish the effective SNR, thereby negatively impacting performance as seen by poorer QuickSIN scores.
Comparison of urinary TIMP-2 and IGFBP7 cut-offs to predict acute kidney injury in critically ill patients

Abstract Background: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are recently identified urinary biomarkers of acute kidney injury (AKI) in critically ill patients. Because their predictive accuracies vary widely, a meta-analysis was performed to evaluate the accuracy of previously reported urinary TIMP-2 and IGFBP7 cut-offs for predicting AKI. Methods: This meta-analysis was reported following the guideline of PRISMA. Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 by 2 investigators, who independently selected studies, extracted relevant data, and evaluated study quality. A bivariate model was used to calculate the pooled estimates. Results: The search identified 5 studies with 1619 critically ill patients. Urinary TIMP-2 and IGFBP7 cut-off points of 0.3 (ng/ml)2/1000 had a sensitivity of 0.89 [95% confidence interval (CI) 0.85–0.93], a specificity of 0.48 (95% CI 0.45–0.51) and a diagnostic odds ratio (DOR) of 8.33 (95% CI 5.55–12.52). The area under the curve (AUC) estimated by the summary receiver operating characteristic (SROC) curve was 0.748. Based on 891 critically ill patients from 4 studies, urinary TIMP-2 and IGFBP7 cut-off points of 2.0 (ng/ml)2/1000 had a sensitivity of 0.45 (95% CI 0.37–0.53), a specificity of 0.93 (95% CI 0.91–0.95) and a DOR of 11.43 (95% CI 7.43–17.57). The AUC estimated by SROC was 0.844. Conclusion: Cut-off values around 0.3 (ng/ml)2/1000 (high sensitivity) and 2.0 (ng/ml)2/1000 (high specificity) could be accurate surrogate biomarkers predicting AKI in critically ill patients. The urinary TIMP-2 and IGFBP7 cut-off point of 2.0 (ng/mL)2/1000 appears to have the highest overall accuracy. Trial registration: PROSPERO registration number 2018: CRD42018084457 Registered on 11 February 2018.
Global mitigation potential of carbon stored in harvested wood products

Significance Carbon stored within harvested wood products (HWPs) may be a tool to mitigate climate change, yet its global potential as a carbon sink is unknown and difficult to assess. We show that the global HWP pool was a net sink of 335 Mt of CO2 equivalent (CO2e)⋅y−1 in 2015 and as much as 441 Mt of CO2e⋅y−1 by 2030, offsetting substantial amounts of industrial process emissions, but only in some countries, and the global contribution is minor, even in a scenario of favorable conditions. Furthermore, economic shocks can turn a country’s HWP pool into a net source of carbon. In conclusion, carbon stored within end-use HWPs varies widely across countries and depends on evolving market forces. Carbon stored in harvested wood products (HWPs) can affect national greenhouse gas (GHG) inventories, in which the production and end use of HWPs play a key role. The Intergovernmental Panel on Climate Change (IPCC) provides guidance on HWP carbon accounting, which is sensitive to future developments of socioeconomic factors including population, income, and trade. We estimated the carbon stored within HWPs from 1961 to 2065 for 180 countries following IPCC carbon-accounting guidelines, consistent with Food and Agriculture Organization of the United Nations (FAOSTAT) historical data and plausible futures outlined by the shared socioeconomic pathways. We found that the global HWP pool was a net annual sink of 335 Mt of CO2 equivalent (CO2e)⋅y−1 in 2015, offsetting substantial amounts of industrial processes within some countries, and as much as 441 Mt of CO2e⋅y−1 by 2030 under certain socioeconomic developments. Furthermore, there is a considerable sequestration gap (71 Mt of CO2e⋅y−1 of unaccounted carbon storage in 2015 and 120 Mt of CO2e⋅y−1 by 2065) under current IPCC Good Practice Guidance, as traded feedstock is ineligible for national GHG inventories. However, even under favorable socioeconomic conditions, and when accounting for the sequestration gap, carbon stored annually in HWPs is <1% of global emissions. Furthermore, economic shocks can turn the HWP pool into a carbon source either long-term—e.g., the collapse of the USSR—or short-term—e.g., the US economic recession of 2008/09. In conclusion, carbon stored within end-use HWPs varies widely across countries and depends on evolving market forces.
Decreased Temperature Sensitivity of Vestigial Gene Expression in Temperate Populations of Drosophila melanogaster

Drosophila melanogaster recently spread from its tropical origin in Africa and became a cosmopolitan species that has adapted to a wide range of different thermal environments, including temperate climates. An important limiting factor of temperate climates has probably been their low and varying temperatures. The transcriptional output of genes can vary across temperatures, which might have been detrimental while settling in temperate environments. The reduction of temperature-sensitive expression of functionally important genes to ensure consistent levels of gene expression might have been relevant while adapting to such environments. In this study, we focus on the gene vestigial (vg) whose product is a key factor in wing development. We provide evidence that temperature-sensitivity of vg has been buffered in populations from temperate climates. We investigated temperature-sensitivity of vg gene expression in six natural populations, including four temperate populations (three from Europe and one from high-altitude Africa), and two tropical populations from the ancestral species range. All temperate populations exhibited a lower degree of temperature-induced expression plasticity than the tropical populations.
EXTRACTION-BASED TEXT SUMMARIZATION USING FUZZY

Due to the explosive growth of the world-wide web, automatic text summarization has become an essential tool for web users. In this paper we present a novel approach for creating text summaries. Using fuzzy logic and word-net, our model extracts the most relevant sentences from an original document. The approach utilizes fuzzy measures and inference on the extracted textual information from the document to find the most significant sentences. Experimental results reveal that the proposed approach extracts the most relevant sentences when compared to other commercially available text summarizers. Text pre-processing based on word-net and fuzzy analysis is the main part of our work.
Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells

Significance From an interspecies study, we identified and validated downstream targets of the MYC oncogene and demonstrate the conserved role of aminoacyl-tRNA synthetases (aaRSs) in MYC-driven growth. We also tested aaRS inhibitors and describe their potential as therapeutic agents to selectively target MYC-driven cancers. By interfering with protein synthesis, we create a catastrophic situation in which the translation machinery is incapable of handling the increased demand triggered by the pro-growth oncogenic program. This provides a general principle for the design of therapeutic approaches to tumorigenesis. Aberrant MYC oncogene activation is one of the most prevalent characteristics of cancer. By overlapping datasets of Drosophila genes that are insulin-responsive and also regulate nucleolus size, we enriched for Myc target genes required for cellular biosynthesis. Among these, we identified the aminoacyl tRNA synthetases (aaRSs) as essential mediators of Myc growth control in Drosophila and found that their pharmacologic inhibition is sufficient to kill MYC-overexpressing human cells, indicating that aaRS inhibitors might be used to selectively target MYC-driven cancers. We suggest a general principle in which oncogenic increases in cellular biosynthesis sensitize cells to disruption of protein homeostasis.
Infectious Complications After Open Cranial Vault Remodeling for Craniosynostosis.

BACKGROUND Surgical site infection (SSI) after open cranial vault reconstruction (CVR), while relatively uncommon, has received little attention in the literature to date. Here, the authors report our institution's experience with the perioperative management of infectious complications following CVR for craniosynostosis and present the first systematic review of the literature on this topic. METHODS The authors performeda retrospective chart review for patients with syndromic and nonsyndromic craniosynostosis who underwent open CVR between 1990 and 2015 at a single institution to determine predictors of SSIs anda systematic review of studies that evaluated for SSI after CVR to ascertain the pooled incidence of SSI, common infectious organisms, and prophylactic antibiotic protocols. :RESULTS:: Out of 548 primary and 163 secondary CVR cases at our institution, 6 primary reconstruction patients (1.09%) and 9 secondary reconstruction patients (5.52%) developed an SSI requiring extended hospital stay or readmission (P <0.001); overall infection rate was 2.11%. Streptococcus and Staphylococcus species were the most common organisms isolated. On multivariate analysis, syndromic status conferred more than 7 times greater odds of SSI (OR 7.7, P = 0.023). Pooled analysis of the literature yielded an overall SSI rate of 1.05% to 2.01%. In contrast to our institutional findings, the most common organisms reported were Candida species and Pseudomonas aeruginosa. The most common prophylactic antibiotic protocol was a first-generation cephalosporin for 24 to 72 hours post-operatively. CONCLUSIONS Patients undergoing secondary reconstruction have higher infection rates after CVR, and syndromic status is an important predictor of infection when controlling for other patient factors. Our literature review reveals nosocomial organisms to be the most commonly reported source of infection, though this is contrary to our institutional findings of skin flora being most common. Antibiotic prophylaxis varies institutionally.