Miracle-dz/UniFAR-FTUs huggingface dataset:
An Aqueous Extract of Herbal Medicine ALWPs Enhances Cognitive Performance and Inhibits LPS-Induced Neuroinflammation via FAK/NF-κB Signaling Pathways

Recent studies have shown that Liuwei Dihuang pills (LWPs) can positively affect learning, memory and neurogenesis. However, the underlying molecular mechanisms are not understood. In the present study, we developed ALWPs, a mixture of Antler and LWPs, and investigated whether ALWPs can affect neuroinflammatory responses. We found that ALWPs (500 mg/ml) inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine IL-1β mRNA levels in BV2 microglial cells but not primary astrocytes. ALWPs significantly reduced LPS-induced cell-surface levels of TLR4 to alter neuroinflammation. An examination of the molecular mechanisms by which ALWPs regulate the LPS-induced proinflammatory response revealed that ALWPs significantly downregulated LPS-induced levels of FAK phosphorylation, suggesting that ALWPs modulate FAK signaling to alter LPS-induced IL-1β levels. In addition, treatment with ALWPs followed by LPS resulted in decreased levels of the transcription factor NF-κB in the nucleus compared with LPS alone. Moreover, ALWPs significantly suppressed LPS-induced BV2 microglial cell migration. To examine whether ALWPs modulate learning and memory in vivo, wild-type C57BL/6J mice were orally administered ALWPs (200 mg/kg) or PBS daily for 3 days, intraperitoneally injected (i.p.) with LPS (250 μg/kg) or PBS, and assessed in Y maze and NOR tests. We observed that oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly rescued short- and long-term memory. More importantly, oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly reduced microglial activation in the hippocampus and cortex. Taken together, our results suggest that ALWPs can suppress neuroinflammation-associated cognitive deficits and that ALWPs have potential as a drug for neuroinflammation/neurodegeneration-related diseases, including Alzheimer’s disease (AD).
Abnormal CSF amyloid-β42 and tau levels in hip fracture patients without dementia

Background There is strong association of Alzheimer’s disease (AD) pathology with gait disorder and falls in older adults without dementia. The goal of the study was to examine the prevalence and severity of AD pathology in older adults without dementia who fall and sustain hip fracture. Methods Cerebrospinal fluid (CSF) was obtained from 168 hip fracture patients. CSF Aβ42/40 ratio, p-tau, and t-tau measures were dichotomized into normal vs. abnormal, and categorized according to the A/T/N classification. Results Among the hip fracture patients, 88.6% of the cognitively normal (Clinical Dementia Rating-CDR 0; n = 70) and 98.8% with mild cognitive impairment (CDR 0.5; n = 81) fell in the abnormal biomarker categories by the A/T/N classification. Conclusions A large proportion of older hip fracture patients have CSF evidence of AD pathology. Preoperative determination of AD biomarkers may play a crucial role in identifying persons without dementia who have underlying AD pathology in perioperative settings.
Diversity maximization in doubling metrics

Diversity maximization is an important geometric optimization problem with many applications in recommender systems, machine learning or search engines among others. A typical diversification problem is as follows: Given a finite metric space $(X,d)$ and a parameter $k \in \mathbb{N}$, find a subset of $k$ elements of $X$ that has maximum diversity. There are many functions that measure diversity. One of the most popular measures, called remote-clique, is the sum of the pairwise distances of the chosen elements. In this paper, we present novel results on three widely used diversity measures: Remote-clique, remote-star and remote-bipartition. Our main result are polynomial time approximation schemes for these three diversification problems under the assumption that the metric space is doubling. This setting has been discussed in the recent literature. The existence of such a PTAS however was left open. Our results also hold in the setting where the distances are raised to a fixed power $q\geq 1$, giving rise to more variants of diversity functions, similar in spirit to the variations of clustering problems depending on the power applied to the distances. Finally, we provide a proof of NP-hardness for remote-clique with squared distances in doubling metric spaces.
No Multiplication? No Floating Point? No Problem! Training Networks for Efficient Inference

For successful deployment of deep neural networks on highly--resource-constrained devices (hearing aids, earbuds, wearables), we must simplify the types of operations and the memory/power resources used during inference. Completely avoiding inference-time floating-point operations is one of the simplest ways to design networks for these highly-constrained environments. By discretizing both our in-network non-linearities and our network weights, we can move to simple, compact networks without floating point operations, without multiplications, and avoid all non-linear function computations. Our approach allows us to explore the spectrum of possible networks, ranging from fully continuous versions down to networks with bi-level weights and activations. Our results show that discretization can be done without loss of performance and that we can train a network that will successfully operate without floating-point, without multiplication, and with less RAM on both regression tasks (auto encoding) and multi-class classification tasks (ImageNet). The memory needed to deploy our discretized networks is less than one third of the equivalent architecture that does use floating-point operations.
Nonlinear stochastic receding horizon control: stability, robustness and Monte Carlo methods for control approximation

ABSTRACT This work considers the stability of nonlinear stochastic receding horizon control when the optimal controller is only computed approximately. A number of general classes of controller approximation error are analysed including deterministic and probabilistic errors and even controller sample and hold errors. In each case, it is shown that the controller approximation errors do not accumulate (even over an infinite time frame) and the process converges exponentially fast to a small neighbourhood of the origin. In addition to this analysis, an approximation method for receding horizon optimal control is proposed based on Monte Carlo simulation. This method is derived via the Feynman–Kac formula which gives a stochastic interpretation for the solution of a Hamilton–Jacobi–Bellman equation associated with the true optimal controller. It is shown, and it is a prime motivation for this study, that this particular controller approximation method practically stabilises the underlying nonlinear process.
Automated blood pressure self-measurement station compared to office blood pressure measurement for first trimester screening of pre-eclampsia

Background: Preeclampsia is a serious medical disorder affecting pregnancy. Screening in early pregnancy can identify women at risk and enable effective prophylactic treatment. Accurate blood pressure (BP) measurement is an important element of the screening algorithm. Automated self-screening, while attending the first trimester ultra sound scan, using a BP self-measurement (BPSM) station, could be a low-cost alternative to office BP measurements (OBPM) on both arms performed by clinical staff, if the measurement quality can be ensured. Objectives: The aim of this study was to compare automated BPSM using a self-measurement station on one arm, with OBPM performed by clinical staff on both arms. Primary outcome was the difference in mean arterial pressure (MAP) between the two methods and secondary outcomes were safety and practicality issues. Methods: Pregnant women attending ultrasound-examination at 12 weeks gestational age were recruited and randomized to start with having two OBPMs taken on both arms by staff, using two standard validated automatic upper arm BP devices, or self-measuring using an automated BPSM station following a crossover study design. The BPSM station consists of a validated blood pressure device, and an add-on sensor system capable of registering blood pressure values, rest-time, back-supported, legs-crossed, and ambient noise-levels respectively, and providing interactive guidance during the measurement process, for supporting the self-measurement process. Results: A total of 80 complete BP measurement sets were obtained, for a total of 240 BPSM measurements and 320 OBPM measurements. We found no significant difference between the OBPM and BPSM methods (p=0.86) for mean arterial pressure (MAP). However, erroneous measurements were observed frequently during the experiment, mainly during the first of the 3 BPSM measurements (6%), secondary during the second BPSM measurement (3%). Only one data set (1%) was excluded due to OBPM errors. Conclusion: No significant difference in MAP between the two methods was found. Means for detecting and repeating erroneous BP measurements should be implemented. Measurement errors was found in 9 % of the measurement sets which is not acceptable for clinical use. Thus, several measures have been identified in order to properly identify and recover from such measurement errors in the future.
Central Bank Communication and the Yield Curve: A Semi-Automatic Approach using Non-Negative Matrix Factorization

Communication is now a standard tool in the central bank's monetary policy toolkit. Theoretically, communication provides the central bank an opportunity to guide public expectations, and it has been shown empirically that central bank communication can lead to financial market fluctuations. However, there has been little research into which dimensions or topics of information are most important in causing these fluctuations. We develop a semi-automatic methodology that summarizes the FOMC statements into its main themes, automatically selects the best model based on coherency, and assesses whether there is a significant impact of these themes on the shape of the U.S Treasury yield curve using topic modeling methods from the machine learning literature. Our findings suggest that the FOMC statements can be decomposed into three topics: (i) information related to the economic conditions and the mandates, (ii) information related to monetary policy tools and intermediate targets, and (iii) information related to financial markets and the financial crisis. We find that statements are most influential during the financial crisis and the effects are mostly present in the curvature of the yield curve through information related to the financial theme.
Mutations of genes including DNMT3A detected by next-generation sequencing in thyroid cancer

ABSTRACT More than 90% of thyroid cancer belongs to the papillary and follicular thyroid carcinomas based on pathological subtypes. Papillary and follicular thyroid carcinoma are generally associated with a good prognosis. In contrast, other pathological subtypes such as poorly-differentiated and anaplastic thyroid carcinoma (PDTC and ATC) have a poor clinical outcome with a short life expectancy. To identify the genetic variations and biomarkers that may potentially distinguish the aggressive form of thyroid cancer, we performed a retrospective analysis of the formalin-fixed paraffin-embedded tumor samples from 50 patients who mainly displayed aggressive thyroid cancer using next-generation sequencing of 416 solid tumor-related genes. We adopted extensive bioinformatic analysis to vigorously remove germline single-nucleotide polymorphism and systematic sequencing errors, and report here that mutation in DNMT3A gene was significantly enriched in patients with PDTC or ATC.
Fuzi and Banxia Combination, Eighteen Antagonisms in Chinese Medicine, Aggravates Adriamycin-Induced Cardiomyopathy Associated with PKA/β2AR-Gs Signaling

Aconite Lateralis Radix Praeparata (Fuzi) and Pinelliae Rhizoma (Banxia) are a combination often used to treat cardiovascular diseases in ancient and modern clinical practice. However, eighteen antagonisms based on traditional Chinese medicine (TCM) theory often abided against such combination therapy. Therefore, exploring whether coadministration of the two herbs can be used in adriamycin- (ADR-) induced cardiomyopathy and clarifying the potential mechanism could help to guide its clinical application. Echocardiography experiments revealed that either Fuzi, Banxia, or their combination had effect on ADR-induced heart dysfunction, while high dose Fuzi exerted positive inotropic effect associated with restored PKA levels. Moreover, low dose Fuzi significantly reduced QT/QTc prolongation, inhibited cardiac apoptosis, and upregulated protein expression of PKA. However, combination of Fuzi and Banxia greatly aggravated QT/QTc prolongation and cardiomyocyte apoptosis in ADR rats compared with each drug alone, which was accompanied by a marked decrease in PKA, pSer346 levels. Similarly, Banxia alone treatment promoted cardiac apoptosis and downregulated protein levels of PKA and pSer346. Additionally, high dose Fuzi treatment also produced proapoptotic effect. Taken together, our study has provided the first direct evidence that combination of Fuzi, a positive inotropic agent, with Banxia promoted cardiac apoptosis in an ADR induced rat model of cardiomyopathy, which may be associated with suppression of PKA/β2AR-Gs signaling. This study also provides scientific language for better understanding of the risks and limitations of combination of Fuzi and Banxia in clinical applications.
Financial incentives for objectively-measured physical activity or weight loss in adults with chronic health conditions: A meta-analysis

Objective We conducted a meta-analysis and systematic review of published randomized controlled trials (RCTs) to evaluate the impact of financial incentives (FI) on objectively-measured physical activity (PA) and weight loss (WL) in adults with sedentary behavior or chronic health conditions. Evidence review We performed a systematic search for RCTs published in English indexed in PubMed, Embase, or Web of Science through July 27, 2017. We limited our search to RCTs that involved an FI intervention with a monetary component, objectively-measured PA or WL outcomes, samples with either sedentary lifestyles or chronic health conditions, and a comparator group that did not receive performance-contingent FI. We calculated the mean difference and standardized mean difference (SMD) for each study and used a random effects model to summarize intervention efficacy. We used the Jadad scoring tool to assess the quality of the identified articles. Results We abstracted data from 11 RCTs. Two of the 11 included studies focused on PA, totaling 126 intervention and 116 control subjects. Nine RCTs evaluated the effect of FI on WL, totaling 1,799 intervention and 1,483 control subjects. The combined estimate for change in daily steps was 940 (95%CI [306–1,574]) more in PA intervention groups than in control groups and 2.36 (95%CI [1.80–2.93]) more kilograms lost by WL intervention groups compared to control groups. The overall estimated SMD for both outcomes combined was 0.395 (95%CI [0.243–0.546; p<0.001]), favoring FI interventions. Conclusion FI interventions are efficacious in increasing PA and WL in adults with chronic conditions or sedentary adults. Public health programs to increase PA or prevent chronic disease should consider incorporating FI to improve outcomes.
Neurohormonal Regulation of Appetite and its Relationship with Stress: A Mini Literature Review

Stress has long been known to affect eating behaviors in humans. Stress-induced hyperphagia is considered a potential cause for the development of obesity. Given the high prevalence of obesity and its association with other cardiovascular and metabolic disorders, the subject of stress-induced eating has become even more important. We reviewed data from past studies to further elucidate the relationship between stress, appetite regulation and eating patterns in humans. Even though it is difficult to say with certainty that a person exposed to stress will undereat or overeat, but certain assumptions can be made. Generally, acute stress results in decreased eating whereas chronic stress results in increased eating. Glucocorticoids, the effector molecules of the stress response, increase the tendency to consume high-calorie, palatable foods. Further studies that can link the biological markers of stress-response with the hormones and neurotransmitters of appetite regulation can broaden our understanding of the subject. These studies can provide a groundwork for the development of effective anti-obesity strategies.
Clioquinol is a promising preventive morphological switching compound in the treatment of Candida infections linked to the use of intrauterine devices

Purpose. Candida biofilm infections are frequently linked to the use of biomaterials and are of clinical significance because they are commonly resistant to antifungals. Clioquinol is an antiseptic drug and is effective against multidrug‐resistant Candida. We investigated the effect of clioquinol and two other 8‐hydroxyquinoline derivatives on Candida biofilm. Methodology. The ability to inhibit biofilm formation, inhibit preformed biofilm and remove established biofilms was evaluated using in vitro assays on microtitre plates. The action of clioquinol on biofilm in intrauterine devices (IUDs) was also investigated, describing the first protocol to quantify the inhibitory action of compounds on biofilms formed on IUDs. Results. Clioquinol was found to be the most effective 8‐hydroxyquinoline derivative among those tested. It prevented more than 90 % of biofilm formation, which can be attributed to blockade of hyphal development. Clioquinol also reduced the metabolic activity of sessile Candida but the susceptibility was lower compared to planktonic cells (0.031‐0.5 &mgr;g ml‐1 required to inhibit 50 % planktonic cells and 4‐16 &mgr;g ml‐1 to inhibit 50 % preformed biofilms). On the other hand, almost complete removal of biofilms was not achieved for the majority of the isolates. Candida spp. also showed the ability to form biofilm on copper IUD; clioquinol eradicated 80‐100 % of these biofilms. Conclusion. Our results indicate a potential application in terms of biomaterials for 8‐hydroxyquinoline derivatives. Clioquinol could be used as a coating to prevent morphological switching and thus prevent biofilm formation. Furthermore, clioquinol may have future applications in the treatment of Candida infections linked to the use of IUDs.
Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents?

Effective therapies for relapsed/refractory meningioma after surgery and radiation therapy represent an unmet need. Most meningiomas are highly vascularized tumors and, therefore, potentially amenable to antiangiogenic therapy. Herein, we review comprehensively the scientific literature on systemic therapy options for relapsed, persistent or metastatic meningioma, not amenable to local therapy. Also, this review offers insights into the function of vascular endothelial growth factor/receptor pathway both in health and disease. Further, we address the current status of the preclinical and clinical studies targeting vascular endothelial growth factor/receptor signaling in meningioma. Most relevant publications were identified through searching the PubMed/Medline database for articles published from inception to 1 February 2018. Vascular endothelial growth factor pathway activation might represent the primary driver of angiogenesis in meningioma. Positive findings of two prospective phase II trials, supported by the results of several retrospective cohorts, suggest a clinical benefit for the vascular endothelial growth factor inhibitor bevacizumab in refractory meningioma. Bevacizumab causes both peritumoral brain edema reduction and true meningioma shrinkage. Patients with WHO grades II–III meningioma appear to benefit more than patients with grade I disease. Similarly, responses have been documented with certain oral targeted anti-vascular endothelial growth factor/receptor agents. Further exploration of the role of vascular endothelial growth factor/receptor inhibitors in refractory meningioma seems warranted.
Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field.

Whether lipid rafts are present in the membranes of living cells remains hotly disputed despite their incontrovertible existence in liposomes at 298 K. In attempts to resolve this debate, molecular dynamics (MD) simulations have been extensively used to study lipid phase separation at high resolution. However, computation has been of limited utility in this respect because the experimental distributions of phases in lamellar lipid mixtures are poorly reproduced by simulations. In particular, all-atom (AA) approaches suffer from restrictions on accessible time scales and system sizes whereas the more efficient coarse-grained (CG) force fields remain insufficiently accurate to achieve correspondence with experiment. In this work, we refine the CG Martini parameters for the high- and low-melting temperature ( Tm) lipids 1,2-dipalmitoyl- sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dioleoyl- sn-glycero-3-phosphatidylcholine (DOPC). Our approach involves the modification of bonded Martini parameters based on fitting to atomistic simulations conducted with the CHARMM36 lipid force field. The resulting CG parameters reproduce experimental structural and thermodynamic properties of homogeneous lipid membranes while concurrently improving simulation fidelity to experimental phase diagrams of DPPC, DOPC, and cholesterol lipid mixtures. Importantly, the refined parameters provide much better phase accuracy for regions near the critical point that mimic the lipid concentrations under physiological conditions.
ComQA: A Community-sourced Dataset for Complex Factoid Question Answering with Paraphrase Clusters

To bridge the gap between the capabilities of the state-of-the-art in factoid question answering (QA) and what users ask, we need large datasets of real user questions that capture the various question phenomena users are interested in, and the diverse ways in which these questions are formulated. We introduce ComQA, a large dataset of real user questions that exhibit different challenging aspects such as compositionality, temporal reasoning, and comparisons. ComQA questions come from the WikiAnswers community QA platform, which typically contains questions that are not satisfactorily answerable by existing search engine technology. Through a large crowdsourcing effort, we clean the question dataset, group questions into paraphrase clusters, and annotate clusters with their answers. ComQA contains 11,214 questions grouped into 4,834 paraphrase clusters. We detail the process of constructing ComQA, including the measures taken to ensure its high quality while making effective use of crowdsourcing. We also present an extensive analysis of the dataset and the results achieved by state-of-the-art systems on ComQA, demonstrating that our dataset can be a driver of future research on QA.