Miracle-dz/UniFAR-FTUs huggingface dataset:
Phloroglucinol derivatives from Hypericum species trigger mitochondrial dysfunction in Leishmania amazonensis

Abstract Bioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), isouliginosin B (2) and uliginosin B (3) isolated from Hypericum species. Promastigotes and amastigotes of Leishmania amazonensis were incubated with compounds 1–3 at concentrations 1–100 µm for 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1–3 showed high leishmanicidal activity against promastigotes, IC50 values of 10.5, 17.5 and 11.3 µm, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 [Σ fractional inhibitory concentration (FIC) = 0.41], and 2 and 3 (ΣFIC = 0.28) on promastigotes. All Hypericum compounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.
Visual body size norms and the under‐detection of overweight and obesity

The weight status of men with overweight and obesity tends to be visually underestimated, but visual recognition of female overweight and obesity has not been formally examined. The aims of the present studies were to test whether people can accurately recognize both male and female overweight and obesity and to examine a visual norm‐based explanation for why weight status is underestimated.
The ARP 2/3 complex mediates endothelial barrier function and recovery

Pulmonary endothelial cell (EC) barrier dysfunction and recovery is critical to the pathophysiology of acute respiratory distress syndrome. Cytoskeletal and subsequent cell membrane dynamics play a key mechanistic role in determination of EC barrier integrity. Here, we characterizAQe the actin related protein 2/3 (Arp 2/3) complex, a regulator of peripheral branched actin polymerization, in human pulmonary EC barrier function through studies of transendothelial electrical resistance (TER), intercellular gap formation, peripheral cytoskeletal structures and lamellipodia. Compared to control, Arp 2/3 inhibition with the small molecule inhibitor CK-666 results in a reduction of baseline barrier function (1,241 ± 53 vs 988 ± 64 ohm; p < 0.01), S1P-induced barrier enhancement and delayed recovery of barrier function after thrombin (143 ± 14 vs 93 ± 6 min; p < 0.01). Functional changes of Arp 2/3 inhibition on barrier integrity are associated temporally with increased intercellular gap area at baseline (0.456 ± 0.02 vs 0.299 ± 0.02; p < 0.05) and thirty minutes after thrombin (0.885 ± 0.03 vs 0.754 ± 0.03; p < 0.05). Immunofluorescent microscopy reveals reduced lamellipodia formation after S1P and during thrombin recovery in Arp 2/3 inhibited cells. Individual lamellipodia demonstrate reduced depth following Arp 2/3 inhibition vs vehicle at baseline (1.83 ± 0.41 vs 2.55 ± 0.46 µm; p < 0.05) and thirty minutes after S1P treatment (1.53 ± 0.37 vs 2.09 ± 0.36 µm; p < 0.05). These results establish a critical role for Arp 2/3 activity in determination of pulmonary endothelial barrier function and recovery through formation of EC lamellipodia and closure of intercellular gaps.
THE ABDUS SALAM INTERNATIONAL CENTRE FOR THEORETICAL PHYSICS ON THE MOTT TRANSITION AND THE NEW METAL-INSULATOR TRANSITIONS IN DOPED COVALENT AND POLAR CRYSTALS

The Mott transition and new metal-insulator transitions (MIT's) and their distinctive features in doped covalent semiconductors and polar compounds are studied within the continuum model of extrinsic carrier self-trapping, the Hubbard impurity band model (with on-site Coulomb repulsion and screening effects) and the extrinsic (bi)polaronic band model (with shortand long-range carrier-impurity, impurity-phonon and carrier-phonon interactions and intercarrier correlation) using the appropriate tight-binding approximations and variational methods. We have shown the formation possibility of large-radius localized oneand two-carrier impurity (or defect) states and narrow impurity bands in the band gap and charge transfer gap of these carrier-doped systems. The extrinsic Mott-Hubbard and (bi)polaronic insulating gaps are calculated exactly. The proper criterions for Mott transition, extrinsic excitonic and (bi)polaronic MIT's are obtained. We have demonstrated that the Mott transition occurs in doped covalent simiconductors (i.e. Si and Ge) and some insulators with weak carrier-phonon coupling near the large-radius dopants. While, in doped polar compounds (e.g. oxide high-Tc superconductors (HTSC) and related materials) the MIT's are new extrinsic (or intrinsic) (bi)polaronic MIT's. We have found that the anisotropy of the dielectric (or (bi)polaronic) properties of doped cuprate HTSC is responsible for smooth (or continuous) MIT's, stripe formation and suppression of highTc superconductivity. Various experimental results on in-gap states, bands and MIT's in doped covalent semiconductors, oxide HTSC and related materials are in good agreement with the developed theory of Mott transition and new (bi)polaronic MIT's.
Polymeric Prosthesis as Acoustic, Pressure, Temperature, and Light Sensor Fabricated by Three-Dimensional Printing

Additional information available the end of the chapter Abstract There have been new developments in prosthetic technology over the past 30 years, and the union of bionics and prosthetics has improved mobility and aesthetics, however, a person who lacks a limb will have to continue without a valuable sense, touch. As a result of stimulation of the receptors under the skin and subcutaneous tissue, touch is sensitive to mechanical stimuli and stimuli that produce heat, cold, and pain. In this chapter, the results presented include the stages of design, construction, and characterization of an ear prosthesis manufactured with a 3D printer in polyvi‐ nylidene fluoride (PVDF), which is a biocompatible and ferroelectric smart material (exhibits piezoelectric and pyroelectric properties). Thus, the behavior of the prosthe‐ sis in response to external stimuli such as pressure, heat, cold, acoustic waves, and light is presented, thereby, extending the purpose of a prosthesis to the area of sensory perception.
Affinity-based distributed algorithm for 3D reconstruction in large scale Visual Sensor Networks

In recent years, Visual Sensor Networks have emerged as an interesting category of distributed sensor-actor systems to retrieve data from the observed scene and produce information. Indeed, the request for accurate 3D scene reconstruction in several applications is leading to the development of very large systems and more specifically to large scale motion capture systems. When dealing with such huge amount of data from a large number of cameras it becomes very hard to make real time reconstruction on a single machine. Within this context, a distributed approach for reconstruction on large scale camera networks is proposed. The approach is based on geometric triangulation performed in a distributed fashion on the computational grid formed by the camera network organized into a tree structure. Since the computational performance of the algorithm strongly depends on the order in which cameras are paired, to optimize the reconstruction a pairing strategy is designed that relies on an affinity score among cameras. This score is computed from a probabilistic perspective by studying the variance of the 3D target reconstruction error and resorting to a normalized cut graph partitioning. The scaling laws and the results obtained in simulation suggest that the proposed strategy allows to obtain a significant reduction of the computational time.
The first investigation of Wilms' tumour atomic structure-nitrogen and carbon isotopic composition as a novel biomarker for the most individual approach in cancer disease

The paper describes a novel approach to investigating Wilms' tumour (nephroblastoma) biology at the atomic level. Isotope Ratio Mass Spectrometry (IRMS) was used to directly assess the isotope ratios of nitrogen and carbon in 84 Wilms' tumour tissue samples from 28 cases representing the histological spectrum of nephroblastoma. Marked differences in nitrogen and carbon isotope ratios were found between nephroblastoma histological types and along the course of cancer disease, with a breakout in isotope ratio of the examined elements in tumour tissue found between stages 2 and 3. Different isotopic compositions with regard to nitrogen and carbon content were observed in blastemal Wilms' tumour, with and without focal anaplasia, and in poorly- and well-differentiated epithelial nephroblastoma. This first assessment of nitrogen and carbon isotope ratio reveals the previously unknown part of Wilms' tumour biology and represents a potential novel biomarker, allowing for a highly individual approach to treating cancer. Furthermore, this method of estimating isotopic composition appears to be the most sensitive tool yet for cancer tissue evaluation, and a valuable complement to established cancer study methods with prospective clinical impact.
Assessment of the Quality of Reporting in Abstracts of Randomized Controlled Trials Published in Five Leading Chinese Medical Journals

Background Clear, transparent and sufficiently detailed abstracts of randomized trials (RCTs), published in journal articles are important because readers will often base their initial assessment of a trial on such information. However, little is known about the quality of reporting in abstracts of RCTs published in medical journals in China. Methods We identified RCTs abstracts from 5 five leading Chinese medical journals published between 1998 and 2007 and indexed in MEDLINE. We assessed the quality of reporting of these abstracts based on the Consolidated Standards of Reporting Trials (CONSORT) abstract checklist. We also sought to identify whether any differences exist in reporting between the Chinese and English language version of the same abstract. Results We identified 332 RCT abstracts eligible for examination. Overall, the abstracts we examined reported 0–8 items as designated in the CONSORT checklist. On average, three items were reported per abstract. Details of the interventions (288/332; 87%), the number of participants randomized (216/332; 65%) and study objectives (109/332; 33%) were the top three items reported. Only two RCT abstracts reported details of trial registration, no abstracts reported the method of allocation concealment and only one mentioned specifically who was blinded. In terms of the proportion of RCT abstracts fulfilling a criterion, the absolute difference (percentage points) between the Chinese and English abstracts was 10% (ranging from 0 to 25%) on average, per item. Conclusions The quality of reporting in abstracts of RCTs published in Chinese medical journals needs to be improved. We hope that the introduction and endorsement of the CONSORT for Abstracts guidelines by journals reporting RCTs will lead to improvements in the quality of reporting.
RFX1 maintains testis cord integrity by regulating the expression of Itga6 in male mouse embryos

Formation and maintenance of testis cords during embryogenesis are essential for establishing testicular structure and function in adults. At least five genes (Wt1, Dhh, Sox8/Sox9, and Dax1) appear to be required for the maintenance of testis cord integrity in mice. Here, we report that RFX1 is specifically expressed in fetal Sertoli cells. Mouse embryos conditionally deficient in Rfx1 (Rfx1flox/flox, Amh‐Cre) possessed disrupted testis cords, as the basal lamina lining was fragmented or completely absent in some areas of the testes. Spermatogenesis was blocked, leading to complete infertility. Expression of integrin alpha‐6 was significantly decreased in Rfx1‐deficient testes compared to control testes; indeed, luciferase and chromatin immunoprecipitation assays indicated that RFX1 directly activates transcription of Itga6 (the gene coding for integrin alpha‐6). Taken together, RFX1 transcriptionally targets Itga6 in Sertoli cells, thereby, helping maintain the integrity of the basal lamina during testis cord development. Mol. Reprod. Dev. 83: 606–614, 2016. © 2016 Wiley Periodicals, Inc.
Protein phosphatase Mg2+/Mn2+ dependent 1F promotes smoking-induced breast cancer by inactivating phosphorylated-p53-induced signals

We previously demonstrated that the activation of α9-nicotinic acetylcholine receptor (α9-nAchR) signaling by smoking promotes breast cancer formation. To investigate the downstream signaling molecules involved in α9-nAChR-induced breast tumorigenesis, we used real-time polymerase chain reactions and Western blotting to assess expression of protein phosphatase Mg2+/Mn2+ dependent 1F (PPM1F), a Ser/Thr protein phosphatase, in human breast cancer samples (n=167). Additionally, stable PPM1F-knockdown and -overexpressing cell lines were established to evaluate the function of PPM1F. The phosphatase activity of PPM1F in nicotine-treated cells was assessed through Western blotting, confocal microscopy, and fluorescence resonance energy transfer. Higher levels of PPM1F were detected in the breast cancer tissues of heavy smokers (n=7, 12.8-fold) greater than of non-smokers (n= 28, 6.3-fold) (**p=0.01). In vitro, nicotine induced PPM1F expression, whereas α9-nAChR knockdown reduced the protein expression of PPM1F. A series of biochemical experiments using nicotine-treated cells suggested that the dephosphorylation of p53 (Ser-20) and BAX (Ser-184) by PPM1F is a critical posttranslational modification, as observed in breast cancer patients who were heavy smokers. These observations indicate that PPM1F may be a mediator downstream of α9-nAChR that activates smoking-induced carcinogenic signals. Thus, PPM1F expression could be used for prognostic diagnosis or inhibited for cancer prevention and therapy.
Biological therapies targeting arrhythmias: are cells and genes the answer?

ABSTRACT Introduction: Arrhythmias can cause symptoms ranging from simple dizziness to life-threatening circulatory collapse. Current management includes medical therapy and procedures such as catheter ablation or device implantation. However, these strategies still pose a risk of serious side effects, and some patients remain symptomatic. Advancement in our understanding of how arrhythmias develop on the cellular level has made more targeted approaches possible. In addition, contemporary studies have found that several genes are involved in the pathogenesis of arrhythmias. Areas covered: In the present review, the authors explore the cellular and genetic mechanisms leading to arrhythmias as well as the progress that has been made in using both gene and cell therapy to treat tachy- and bradyarrhythmias. They also consider why gene and cell therapy has resulted into a few clinical trials with promising results, however still not applicable in routine clinical practice. Expert opinion: The question currently is whether such biological therapies could replace current established approaches. The contemporary evidence suggests that despite recent advances in this field, it will need more work in experimental models before this is applied into clinical practice. Gene and cell studies targeting conduction and repolarization are promising, but still not ready for use in the clinical setting.
Identification of unique venous thromboembolism-susceptibility variants in African-Americans

Summary To identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype. Among 393 AA VTE cases and 4,941 AA controls, three intragenic SNPs reached genome-wide significance: LEMD3 rs138916004 (OR=3.2; p=1.3E-08), LY86 rs3804476 (OR=1.8; p=2E-08) and LOC100130298 rs142143628 (OR=4.5; p=4.4E-08); all three SNPs validated using internal cross-validation, parametric bootstrap and meta-analysis methods. LEMD3 rs138916004 and LOC100130298 rs142143628 are only present in Africans (1000G data). LEMD3 showed a significant differential expression in both NCBI Gene Expression Omnibus (GEO) and the Mayo Clinic gene expression data, LOC100130298 showed a significant differential expression only in the GEO expression data, and LY86 showed a significant differential expression only in the Mayo expression data. LEMD3 encodes for an antagonist of TGF-β-induced cell proliferation arrest. LY86 encodes for MD-1 which down-regulates the pro-inflammatory response to lipopolysaccharide; LY86 variation was previously associated with VTE in white women; LOC100130298 is a non-coding RNA gene with unknown regulatory activity in gene expression and epigenetics. Supplementary Material to this article is available online at www.thrombosis-online.com.
A Hybrid Implementation of Two-Level Domain Decomposition Algorithm for Solving Elliptic Equation on CPU/GPUs

The rapid compute hardware development has shifted to the hybrid architecture consisting of both CPUs and GPUs. For the class of problems described by partial differential equations (PDEs) discretized by finite difference or finite element methods, obtaining reasonably good performance on a CPU/GPU platform is still a challenge. In this paper, we propose and test an algorithm with several building layers matching the hybrid architecture. The scalability of the approach is obtained by a two-level domain decomposition method, and the GPU performance is effectuated by using various local multigrid methods with suitable smoothers. Efficiency and scalability of our algorithm are demonstrated by convincing performance analysis on a hybrid platform of CPU/GPU.
Comparison of the Effectiveness of Whole Body Vibration in Stroke Patients: A Meta-Analysis

Objectives The goals of this study were to assess the effectiveness of WBV (whole body vibration) training through an analysis of effect sizes, identify advantages of WBV training, and suggest other effective treatment methods. Methods Four databases, namely, EMBASE, PubMed, EBSCO, and Web of Science, were used to collect articles on vibration. Keywords such as “vibration” and “stroke” were used in the search for published articles. Consequently, eleven studies were selected in the second screening using meta-analyses. Results The total effect size of patients with dementia in the studies was 0.25, which was small. The effect size of spasticity was the greatest at 1.24 (high), followed by metabolism at 0.99 (high), balance, muscle strength, gait, and circulation in the decreasing order of effect size. Conclusions The effect sizes for muscle strength and balance and gait function, all of which play an important role in performance of daily activities, were small. In contrast, effect sizes for bone metabolism and spasticity were moderate. This suggests that WBV training may provide a safe, alternative treatment method for improving the symptoms of stroke in patients.
Do GPs want or need formal support following a patient suicide?: a mixed methods study.

BACKGROUND Patient suicide can be a devastating event for some general practitioners (GPs). Few guidelines exist to aid or support GPs in the aftermath of patient suicide. AIM To explore GPs views on how they are affected by a patient suicide and the formal support available to them following a patient suicide. DESIGN Questionnaires and semi-structured interviews. SETTING General practices in the northwest of England. METHODS About 198 semi-structured interviews were conducted as part of a retrospective study. Interviews were transcribed verbatim and analysed using descriptive statistics and a framework thematic approach. RESULTS GPs were aged between 31 and 67 years, 144 (73%) were male and the number of years in practice varied between 8 and 40 years (median = 24 years). GPs were based at 133 (67%) urban and 65 (33%) rural practices, 30 (15%) were single-handed GP practices and 168 (85%) practices had two or more GPs. About 131 (66%) GPs reported being affected by patient suicide through feelings of grief, guilt and self-scrutiny. A greater number of years in practice may have been protective against these effects. About 54 (27%) GPs reported having mostly 'informal' support from peers or colleagues and support was less available to younger and single handed GPs. CONCLUSIONS Our findings suggest that the majority of GPs are affected by patient suicide and most seek informal support from their peers and colleagues. Although many indicated that informal support systems were adequate and provided a protective environment, procedures should be developed to ensure the availability of guidelines for those who may require formal support.
Massive MIMO, Non-Orthogonal Multiple Access and Interleave Division Multiple Access

This paper provides an overview on the rationales in incorporating massive multiple-input multiple-output (MIMO), non-orthogonal multiple access (NOMA), and interleave division multiple access (IDMA) in a unified framework. Our emphasis is on multi-user gain that refers to the advantage of allowing multi-user transmission in massive MIMO. Such a gain can potentially offer tens or even hundreds of times of rate increase. The main difficulty in achieving multi-user gain is the reliance on accurate channel state information (CSI) in the existing schemes. With accurate CSI, both OMA and NOMA can deliver performance not far away from capacity. Without accurate CSI, however, most of the existing schemes do not work well. We outline a solution to this difficulty based on IDMA and iterative data-aided channel estimation (DACE). This scheme can offer very high throughput and is robust against the pilot contamination problem. The receiver cost is low, since only maximum ratio combining (MRC) is involved and there is no matrix inversion or decomposition. Under time division duplex, accurate CSI acquired in the up-link can be used to support low-cost down-link solutions, such as zero forcing. These findings offer useful design considerations for future systems.
Fast Large-Scale Approximate Graph Construction for NLP

Many natural language processing problems involve constructing large nearest-neighbor graphs. We propose a system called FLAG to construct such graphs approximately from large data sets. To handle the large amount of data, our algorithm maintains approximate counts based on sketching algorithms. To find the approximate nearest neighbors, our algorithm pairs a new distributed online-PMI algorithm with novel fast approximate nearest neighbor search algorithms (variants of Pleb). These algorithms return the approximate nearest neighbors quickly. We show our system's efficiency in both intrinsic and extrinsic experiments. We further evaluate our fast search algorithms both quantitatively and qualitatively on two NLP applications.