Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug Response in a Preclinical Model of Lymphangioleiomyomatosis / Tuberous Sclerosis Complex

Background: TSC2-deficient cells can proliferate in the lungs, kidneys, and other organs causing devastating progressive multisystem disorders such as lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC). Preclinical models utilizing LAM patient-derived cells have been difficult to establish. We developed a novel animal model system to study the molecular mechanisms of TSC/LAM pathogenesis and tumorigenesis and provide a platform for drug testing. Methods and Findings: TSC2-deficient human cells, derived from the angiomyolipoma of a LAM patient, were engineered to co-express both sodium-iodide symporter (NIS) and green fluorescent protein (GFP). Cells were inoculated intraparenchymally, intravenously, or intratracheally into athymic NCr nu/nu mice and cells were tracked and quantified using single photon emission computed tomography (SPECT) and computed tomography (CT). Surprisingly, TSC2-deficient cells administered intratracheally resulted in rapid dissemination to lymph node basins throughout the body, and histopathological changes in the lung consistent with LAM. Estrogen was found to be permissive for tumor growth and dissemination. Rapamycin inhibited tumor growth, but tumors regrew after the drug treatment was withdrawn. Conclusions: We generated homogeneous NIS/GFP co-expressing TSC2-deficient, patient-derived cells that can proliferate and migrate in vivo after intratracheal instillation. Although the animal model we describe has some limitations, we demonstrate that systemic tumors formed from TSC2-deficient cells can be monitored and quantified noninvasively over time using SPECT/CT, thus providing a much needed model system for in vivo drug testing and mechanistic studies of TSC2deficient cells and their related clinical syndromes. Citation: Liu F, Lunsford EP, Tong J, Ashitate Y, Gibbs SL, et al. (2012) Real-Time Monitoring of Tumorigenesis, Dissemination, & Drug Response in a Preclinical Model of Lymphangioleiomyomatosis/Tuberous Sclerosis Complex. PLoS ONE 7(6): e38589. doi:10.1371/journal.pone. 0038589 Editor: Salvatore V. Pizzo, Duke University Medical Center, United States of America Received August 15, 2011; Accepted May 9, 2012; Published June 15, 2012 Copyright: 2012 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported in part by grants to JVF from the United States National Institutes of Health (High-End Instrumentation Grant #S10-RR023010), the Ellison Foundation, and the Tuberous Sclerosis Alliance. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Competing Interests: The authors have declared that no competing interests exist. * E-mail: jfrangio@bidmc.harvard. edu
From handcrafted to deep local features

This paper presents an overview of the evolution of local features from handcrafted to deep-learning-based methods, followed by a discussion of several benchmarks and papers evaluating such local features. Our investigations are motivated by 3D reconstruction problems, where the precise location of the features is important. As we describe these methods, we highlight and explain the challenges of feature extraction and potential ways to overcome them. We first present handcrafted methods, followed by methods based on classical machine learning and finally we discuss methods based on deep-learning. This largely chronologically-ordered presentation will help the reader to fully understand the topic of image and region description in order to make best use of it in modern computer vision applications. In particular, understanding handcrafted methods and their motivation can help to understand modern approaches and how machine learning is used to improve the results. We also provide references to most of the relevant literature and code.
Title The effects of lender-borrower communication on P 2 P lendingoutcomes

Lenders face great uncertainty because of the information asymmetry problem in peerto-peer (P2P) marketplaces. This paper studies an online feature on a P2P platform, which allows lenders to seek information directly from the borrower of a loan, and examines the impact of the direct lender-borrower communication on the funding outcomes and the loan performance. Our analysis results show that the number of lender comments is negatively associated with funding success. This implies that as a listing receives more comments from lenders, the chance of getting funded is lower. On the other hand, the number of borrower responses and response length are positively associated with funding success, although they cannot help reduce the final interest rate. The role of borrower response is even stronger for listings with poor credit grades. The loan performance (i.e., default ratio), however, cannot be predicted based on the amount of lender-borrower communication.
Mapping urinary chemokines in human lupus nephritis: Potentially redundant pathways recruit CD4+ and CD8+ T cells and macrophages

Renal infiltration of inflammatory cells contributes to the pathogenesis of lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokines were significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity. Analysis of the corresponding receptors revealed abundance of urinary CD8+ T cells for CCR5 and CXCR3, while CD4+ T cells were additionally enriched for CCR1, CCR6 and CXCR6. Urinary Treg showed similar CCR expression, and urinary CD14+ macrophages were enriched for CCR5 expressing cells. In conclusion, cell specific recruitment patterns seem to involve CCR5 and CXCR3 in all cells studied, while CD4+ T‐cell subset recruitment is probably much more varied. However, urinary chemokine abundance in active LN is individually variable in our cohort and does not offer a singular chemokine usable as universal biomarker or potential future treatment target.
Negative self-appraisal mediates the relationship between mindfulness and confidence among adolescent female provincial hockey players in South Africa

Background Mounting evidence suggests that mindfulness is positively related to athletic performance and athlete wellbeing. However, few attempts have been made to explore the psychological processes by which mindfulness might impact performance. Objective To determine whether negative self-appraisal mediates the relationship between dispositional mindfulness and the confidence component of mental toughness among provincial adolescent female hockey players in South Africa. Methods Provincial adolescent female hockey players (n=486) completed measures of dispositional mindfulness, mental toughness-related confidence and negative self-appraisal. Correlation coefficients were calculated between all variables included in the study. An ordinary least-squares regression analysis was performed to test the indirect effect of negative self-appraisal on the relationship between dispositional mindfulness and confidence. Results Negative self-appraisal exhibited an indirect effect on the relationship between dispositional mindfulness and the confidence component of mental toughness (β = .06, SE = .0, CI95 = .04, .09). A subsequent Soble test confirmed that negative self-appraisal served as a statistically significant mediator (β = .06, SE = .01, Z = 5.76, p = .001) in the model. Furthermore, 78.3% of the variance in the effect of dispositional mindfulness on the confidence component of mental toughness was accounted for by negative self-appraisal. Conclusion The effect of dispositional mindfulness on the confidence component of mental toughness among adolescent athletes is mediated by negative self-appraisal. Based on the current findings, dispositional mindfulness may foster confidence by lessening the impact of rigid negative appraisals of one’s performance and worth as an athlete.
National Community Health Worker Programs: How Can They Be Strengthened?

This article is based on a collaborative research study of policy and practice in national community health worker (CHW) programs in developing countries. The study involved a review of the relevant literature, case studies in Botswana, Colombia and Sri Lanka, and an international workshop where the future of such programs was discussed. The findings of this research are discussed under four headings: unrealistic expectations, poor initial planning, problems of sustainability, and the difficulties of maintaining quality. It is clear that existing national community health worker programs have suffered from conceptual and implementation problems. However, given the interest and political will, governments can address these problems by adopting more flexible approaches within their CHW programs, by planning for them within the context of all health sector activities rather than as a separate activity, and by immediately addressing weaknesses in task allocation, training and supervision. CHWs represent an important health resource, whose potential in extending coverage and providing a reasonable level of care to otherwise underserved populations must be fully tapped.
Freedom, growth, and the environment

A number of recent papers have found that certain measures of pollution worsen and later improve as income per head increases. It is widely believed that the downhill portion of this inverted-U curve reflects an induced policy response; that, as incomes rise, citizens demand improvements in environmental quality, and that these demands are delivered by the political system. In this paper we find that, for a number of pollution variables, an increase in civil and political freedoms significantly improves environmental quality. For other pollution variables, however, we find that freedoms have no effect. The former finding suggests that political reforms may be as important as economic reforms in improving environmental quality worldwide. The latter finding hints that the observation that pollution levels fall with income, once income becomes high enough, may not always reflect an induced policy response.
’ s response to reviews Title : Irreversible electroporation versus radiotherapy after induction chemotherapy on survival in patients with locally advanced pancreatic cancer : a propensity score analysis

Title: Irreversible electroporation versus radiotherapy after induction chemotherapy on survival in patients with locally advanced pancreatic cancer: a propensity score analysis Authors: Chaobin He (hechb@sysucc.org.cn) Jun Wang (wangjun@sysucc.org.cn) Shuxin Sun (sunshx@sysucc.org.cn) Yu Zhang (zhangyu@gzzoc.com) Xiaojun Lin (linxj@sysucc.org.cn) Xiangming Lao (laoxm@sysucc.org.cn) Bokang Cui (cuibk@sysucc.org.cn) Shengping Li (lishp@sysucc.org.cn) Version: 2 Date: 10 Apr 2019 Author’s response to reviews: Dear Chalisa Iamsrithong and reviewers:
S-nitrosoglutathione reductase (GSNOR) enhances vasculogenesis by mesenchymal stem cells

Although nitric oxide (NO) signaling promotes differentiation and maturation of endothelial progenitor cells, its role in the differentiation of mesenchymal stem cells (MSCs) into endothelial cells remains controversial. We tested the role of NO signaling in MSCs derived from WT mice and mice homozygous for a deletion of S-nitrosoglutathione reductase (GSNOR−/−), a denitrosylase that regulates S-nitrosylation. GSNOR−/− MSCs exhibited markedly diminished capacity for vasculogenesis in an in vitro Matrigel tube–forming assay and in vivo relative to WT MSCs. This decrease was associated with down-regulation of the PDGF receptorα (PDGFRα) in GSNOR−/− MSCs, a receptor essential for VEGF-A action in MSCs. Pharmacologic inhibition of NO synthase with L-NG-nitroarginine methyl ester (L-NAME) and stimulation of growth hormone–releasing hormone receptor (GHRHR) with GHRH agonists augmented VEGF-A production and normalized tube formation in GSNOR−/− MSCs, whereas NO donors or PDGFR antagonist reduced tube formation ∼50% by murine and human MSCs. The antagonist also blocked the rescue of tube formation in GSNOR−/− MSCs by L-NAME or the GHRH agonists JI-38, MR-409, and MR-356. Therefore, GSNOR−/− MSCs have a deficient capacity for endothelial differentiation due to downregulation of PDGFRα related to NO/GSNOR imbalance. These findings unravel important aspects of modulation of MSCs by VEGF-A activation of the PDGFR and illustrate a paradoxical inhibitory role of S-nitrosylation signaling in MSC vasculogenesis. Accordingly, disease states characterized by NO deficiency may trigger MSC-mediated vasculogenesis. These findings have important implications for therapeutic application of GHRH agonists to ischemic disorders.
Comparison of key informant and survey methods for ascertainment of childhood epilepsy in West Bengal, India.

BACKGROUND This study aimed to compare efficacy and cost of key informants and survey for ascertainment of childhood epilepsy within a treatment context in rural India. METHODS The study was set in a non-governmental, community programme for the functional and socioeconomic rehabilitation of children with disabilities in rural West Bengal, India. Ascertainment was by two methods: house-to-house survey of 15000 households and also by 430 key informants including village leaders, health workers and 670 schoolchildren. Methods were compared for positive predictive value, and sensitivity by capture-recapture technique. Ninety four children were enrolled into treatment. Predictors of treatment success were determined by multiple logistic regression analysis, giving adjusted odds ratios for remission. The costs of identifying one case and one treatment success were measured by costing personnel, materials and overheads. RESULTS The survey was four times as sensitive as key informants although the positive predictive values were similar (36%, 40%). The survey had an absolute sensitivity of only 59%. Identification by key informants strongly predicted successful treatment outcome (odds ratio [OR] = 4.74, 95% confidence interval [CI] : 1.19-18.85). The cost of finding one case was US$11 and US$14, and of finding one successful treatment outcome US$35 and US$67 for informants and survey respectively. Key informants were essential in attaining longer term programme objectives. CONCLUSIONS In the context of a treatment programme, key informants were the more cost-effective method, but community involvement was traded against low sensitivity in the short term. Overall ascertainment costs were significant in the context of primary health care in India.
Statistical Pattern Recognition: Application to $\nu_{\mu}\to\nu_{\tau}$ Oscillation Searches Based on Kinematic Criteria

Classic statistical techniques (like the multi-dimensional likelihood and the Fisher discriminant method) together with Multi-layer Perceptron and Learning Vector Quantization Neural Networks have been systematically used in order to find the best sensitivity when searching for $\nu_\mu \to \nu_{\tau}$ oscillations. We discovered that for a general direct $\nu_\tau$ appearance search based on kinematic criteria: a) An optimal discrimination power is obtained using only three variables ($E_{visible}$, $P_{T}^{miss}$ and $\rho_{l}$) and their correlations. Increasing the number of variables (or combinations of variables) only increases the complexity of the problem, but does not result in a sensible change of the expected sensitivity. b) The multi-layer perceptron approach offers the best performance. As an example to assert numerically those points, we have considered the problem of $\nu_\tau$ appearance at the CNGS beam using a Liquid Argon TPC detector.
Simultaneous nitrification and denitrification using stored substrate (phb) as the electron donor in an SBR

The potential for PHB (poly‐β‐hydroxybutyrate) to serve as the electron donor for effective simultaneous nitrification and denitrification (SND) was investigated in a 2‐L sequencing batch reactor (SBR) using a mixed culture and acetate as the organic substrate. During the feast period (i.e., acetate present), heterotrophic respiration activity was high and nitrification was prevented due to the inability of nitrifying bacteria to compete with heterotrophs for oxygen. Once acetate was depleted the oxidation rate of PHB was up to 6 times slower than that of soluble acetate and nitrification could proceed due to the decreased competition for oxygen. The slow nature of PHB degradation meant that it was an effective substrate for SND, as it was oxidised at a similar rate to ammonium and was therefore available for SND throughout the entire aerobic period. The percentage of nitrogen removed via SND increased at lower DO concentrations during the famine period, with up to 78% SND achieved at a DO concentration of 0.5 mg L−1. However, the increased percentage of SND at a low DO concentration was compromised by a 2‐times slower rate of nitrogen removal. A moderate DO concentration of 1 mg L−1 was optimal for both SND efficiency (61%) and rate (4.4 mmol N. Cmol X−1 · h−1). Electron flux analysis showed that the period of highest SND activity occurred during the first hour of the aerobic famine period, when the specific oxygen uptake rate (SOUR) was highest. It is postulated that a high SOUR due to NH 4+ and PHB oxidation decreases oxygen penetration into the floc, creating larger zones for anoxic denitrification. The accumulation of nitrate towards the end of the SND period showed that SND was finally limited by the rate of denitrification. As PHB degradation was found to follow first‐order kinetics (dfPHB/dt = −0.19 · fPHB), higher PHB concentrations would be expected to drive SND faster by increasing the availability rate of reducing power and reducing penetration of oxygen into the floc, due to the corresponding increased SOUR. Process control techniques to accumulate higher internal PHB concentrations to improve PHB‐driven SND are discussed. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 706–720, 2003.
EPS Prize Lecture: Characterizing congenital amusia

The ability to make sense of the music in our environment involves sophisticated cognitive mechanisms that, for most people, are acquired effortlessly and in early life. A special population of individuals, with a disorder termed congenital amusia, report lifelong difficulties in this regard. Exploring the nature of this developmental disorder provides a window onto the cognitive architecture of typical musical processing, as well as allowing a study of the relationship between processing of music and other domains, such as language. The present article considers findings concerning pitch discrimination, pitch memory, contour processing, experiential aspects of music listening in amusia, and emerging evidence concerning the neurobiology of the disorder. A simplified model of melodic processing is outlined, and possible loci of the cognitive deficit are discussed.
Knowledge mapping analysis of Ebola research.

OBJECTIVE To reveal the overall situation of research on Ebola virus via visual knowledge mapping analyses of the literatures regarding Ebola virus all around the world, e.g., literature metrology and topic evolvement. METHODS On the basis of the database Web of Knowledge (SCI), a knowledge graph was built by comprehensively utilizing software such as BIBEXCEL, GEPHI, VOSVIEWER, and HistCite. RESULTS According to the results of literature analysis, publications on Ebola virus boomed in 2014, and the research focus transferred gradually from basic research (viral glycoprotein) in 1999 to the prevention and treatment research (vaccine). The United States are in a dominant position in the field of Ebola virus research, wherein the US army (United States Army Medical Research Institute of Infectious Diseases) has the strongest research capacity. DISCUSSION Ebola virus is an important potential biological warfare agent, and some researches may not be published in the form of literature. So the result of literature metrology can only partially reflect the situation of Ebola virus research. In addition, close attention should be paid to the biosafety risk of Ebola research (Tab. 5, Fig. 5, Ref. 14).
Comparative Study of Efficacy of Piperacillin / Tazobactam and Cefoperazone / Sulbactam Combinations in Hospitalised Patients of Complicated Urinary Tract Infections

DOI: 10.21276/sjmps.2018. 4.12. 9 Abstract: Complicated UTIs (cUTIs) are one of the leading causes of the gram negative bacteraemia which occur in patients who have a functionally, metabolically, or anatomically abnormal urinary tract. The primary objective of this study was to compare efficacy of Piperacillin/Tazobactam (PT) and Cefoperazone/Sulbactam (CPS) combinations in complicated Urinary Tract Infections. At entry, total 92 patients admitted in the hospital due to cUTI were enrolled. Among of 92 patients, 49 patients were given PT while 43 patients were given CPS combinations. Clinical symptoms were registered and scored as mild (1) moderate (2) or severe (3). The follow-up were done daily till the patient is discharged. Thereafter, one follow up visit was done within 4 to 9 days of after discharge, termed as test of cure (TOC). Furthermore, one late follow up visit after 6 to 8 weeks was done, known as late follow up visit (LFU). Clinical assessments and microbiological analysis were done at the time of TOC and LFU. The mean baseline clinical score for PT and CPS were 10.89 ± 2.23 and 10.28 ± 2.33, respectively. At TOC visit, PT and CPS groups, clinical scores were 0.86 + 2.35 and 1.36 ± 3.48, respectively; suggesting significant improvement from baseline (p< 0.001). Rate of clinical improvement at TOC visit was 92.68% and 87.50%, while microbiological cure rate was 87.80% and 93.75% with PT and CPS groups respectively. While, at LFU visit, clinical scores in PT and CPS groups were 1.32 + 3.37 and 1.65 + 3.56, respectively, suggesting significant improvement from baseline (p < 0.001). Clinical cure rate at LFU visit was 87.80% and 87.75% while microbiological cure rate at LFU visit was 82.92 and 77.00% in PT and CPS groups, respectively. These results suggest that both regimens have no significant difference for the treatment of cUTI. PT and CPS, both the combinations, are equally efficacious in treatment of cUTI.