Miracle-dz/UniFAR-FTUs huggingface dataset:
Educating coaches about concussion in sports: evaluation of the CDC's "Heads Up: concussion in youth sports" initiative.

BACKGROUND Concussions remain a serious public health concern. It is important that persons involved in youth sports, particularly coaches, be made aware and educated on the signs and symptoms of concussion. This study assessed the perceptions of youth sport coaches who have received the Centers for Disease Control and Prevention's (CDC's) "Heads Up: Concussion in Youth Sports" materials in preventing, recognizing, and responding to concussions. METHODS A 22-item survey was developed with questions pertaining to demographics, awareness of sports-related concussion, and the usefulness of the CDC's "Heads Up: Concussion in Youth Sports" initiative and materials. A total of 340 youth sport coaches completed the survey, for a response rate of 34.0%. RESULTS All youth sport coaches reported having the "Heads Up" materials for approximately 6 months before completing the survey. Seventy-seven percent of youth sports coaches reported being better able to identify athletes who may have a concussion, with 50% reported having learned something new about concussion after reviewing the materials. Sixty-three percent of youth sport coaches viewed concussions as being more serious, while 72% of coaches reporting that they are now educating others on concussion. CONCLUSION The "Heads Up" materials demonstrated that youth sports coaches' were able to appropriately prevent, recognize, and respond to sports-related concussions after reviewing the materials. Future studies should concentrate on evaluating the impact of concussion policies, laws and media coverage on coaches' awareness and prevention, recognition, and response to concussions using a rigorous design including a control group.
HIV status, fertility intentions, and contraception in the era of expanded access to antiretroviral therapy: A case study of rural Mozambique

ABSTRACT Provision of effective contraception to HIV-positive women of reproductive age is critical to effective management of HIV infection and prevention of both vertical and horizontal HIV transmission in developing countries. This exploratory retrospective study examines contraceptive use during the prolonged post-partum period in a sample of 285 HIV-positive and HIV-negative women who gave birth at four rural maternity clinics in a high HIV-prevalence region in Mozambique. Multivariate analyses show no significant variations by HIV status in contraceptive timing (mean time to first contraceptive use of 7.1 months) or prevalence (31% at time of survey) but detect a moderating effect of fertility intentions: while HIV status makes no difference for women wishing to stop childbearing, among women who want to continue having children, or are unsure about their reproductive plans, HIV-positive status is associated with higher likelihood of contraceptive use. Regardless of HIV status, virtually no condom use is reported. These results are situated within the context of a rapidly widening access to post-partum antiretroviral therapy in the study site and similar sub-Saharan settings.
Secreted amyloid precursor proteins promote proliferation and glial differentiation of adult hippocampal neural progenitor cells

Amyloid precursor protein (APP) is an integral membrane glycoprotein present at high levels in nerve cells. Two soluble secreted forms, sAPPα and sAPPβ, are processed from APP by two mutually exclusive proteolytic pathways. sAPPα shows a range of neuroprotective and growth factor properties, including reduction of neuronal injury and improvement in memory performance, in contrast to the generally less potent sAPPβ. In addition, sAPPα has been shown to increase the proliferation of both embryonic neural stem cells and neural progenitor cells (NPCs) derived from the subventricular zone (SVZ) of the adult brain. However, an effect of sAPPα (or sAPPβ) on adult hippocampal progenitor cell proliferation and differentiation has not previously been observed. In this study, we examined the effect of both the α‐ and β‐cleaved ectodomains of sAPP on adult NPCs isolated from the subgranular zone (SGZ) of the rat hippocampus in the presence or absence of depolarizing conditions. Assays were performed to examine the effect of sAPPα and sAPPβ on SGZ‐derived adult NPC proliferation in parallel with SVZ‐derived cells and on differentiation with SGZ‐derived cells. We observed both sAPPα and sAPPβ increased the proliferation of SGZ‐derived NPCs in vitro. Further, treatment of SGZ‐derived NPCs with either sAPPα or sAPPβ increased the number of cells expressing the astrocytic marker GFAP and promoted cell survival. The effect on differential fate was observed in both the presence and absence of depolarizing conditions. Thus, both sAPPα and sAPPβ exert a complex range of effects on SGZ‐derived adult NPCs, including increasing NPC proliferation, maintaining cell viability, yet promoting glial over neuronal differentiation. These findings provide the first direct support for the secreted forms of APP regulating SGZ‐derived NPCs, and raise the possibility some or all of the effects may have therapeutic benefit in models of neurological disease. © 2011 Wiley Periodicals, Inc.
Proteochemometric Modeling of the Inhibition Complexes of Matrix Metalloproteinases with N‐Hydroxy‐2‐[(Phenylsulfonyl)Amino]Acetamide Derivatives Using Topological Autocorrelation Interaction Matrix and Model Ensemble Averaging

A target‐ligand QSAR approach using autocorrelation formalism was developed for modeling the inhibitory potency (pIC50) toward matrix metalloproteinases (MMP‐1, MMP‐2, MMP‐3, MMP‐9, and MMP‐13) of N‐hydroxy‐2‐[(phenylsulfonyl)amino]acetamide derivatives. Target and ligand structural information was encoded in the Topological Autocorrelation Interaction matrix calculated from 2D topological representation of inhibitors and protein sequences. The relevant Topological Autocorrelation Interaction descriptors were selected by genetic algorithm‐based multilinear regression analysis and Bayesian‐regularized genetic neural network approaches. A model ensemble strategy was employed for achieving robust and reliable linear and non‐linear predictors having nine topological autocorrelation interaction descriptors with square correlation coefficients of ensemble test‐set fitting (R2test) about 0.80 and 0.87, respectively. Electrostatic and hydrophobicity/hydrophilicity properties were the most relevant on the optimum models. In addition, the distribution of the inhibition complexes on a self‐organized map depicted target dependence rather than an inhibitor similarity pattern.
Protein kinase C stimulates HuD‐mediated mRNA stability and protein expression of neurotrophic factors and enhances dendritic maturation of hippocampal neurons in culture

HuD protein is an RNA‐binding protein involved in post‐transcriptional regulation of gene expression for synaptogenesis, neuronal differentiation, and learning and memory, and is up‐regulated and redistributed by a protein kinase C (PKC)‐dependent pathway in neurons. Here, we show a PKC‐regulated mechanism on HuD‐mediated mRNA stability and expression of several neurotrophic factors (NTFs) in cultured hippocampal neurons. HuD pull‐down assays showed that HuD is associated with brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin (NT)‐3 mRNAs. Reduction of HuD expression with short hairpin RNAs decreased BDNF, NGF, and NT‐3 mRNAs and NTFs expression. Bryostatin, a PKC activator, treatment enhanced their association with HuD and increased these transcripts' stability. Bryostatin induced HuD phosphorylation, which was inhibited by Ro 32‐0432, a specific PKC inhibitor. Activated PKC specifically phosphorylated coactivator‐associated arginine methyltransferase 1 (CARM1), which methylates HuD and negatively modulates HuD‐mRNA interactions during neuronal differentiation, and inhibited its methyltransferase activity, resulting in decrease in CARM1‐mediated HuD methylation. Furthermore cotreatment of bryostatin and AMI‐1, a specific CARM1 inhibitor, potentiated PKC‐dependent HuD‐mRNA interactions and enhanced dendritic arborization. These results demonstrate that PKC may play an important role in neuronal differentiation and synaptogenesis via stimulating HuD‐mediated mRNA stability and inhibiting CARM1 in hippocampal neurons. © 2012 Wiley Periodicals, Inc.
β blocker treatment is associated with improvement in renal function and anaemia in patients with heart failure

Over the past three decades, there has been rapid progress in the diagnosis and management of patients with chronic congestive heart failure (CHF). However, the mortality from CHF remains high, partly due to comorbidity, the very existence of which may have excluded some patients from previous large-scale clinical trials. Hence, the full effect of modern treatment on non-trial “real life” patients with CHF in clinical practice remains uncertain. Chronic renal impairment (CRI) and anaemia are common comorbidities associated with CHF, and are both independent predictors of poor prognosis.1 It has previously been shown that treatment with either angiotensin-converting enzyme inhibitors (ACEI) or β blockers improves prognosis in patients with CHF with or without CRI.2,3 Among the most recent treatments of CHF, ACEIs are potentially nephrotoxic and may cause worsening of anaemia.3 Thus, the relationship between treatment and outcome in patients with CHF with CRI and anaemia needs further investigation. We aimed to assess the effect of β blocker treatment on renal function and anaemia in consecutive ambulatory patients with CHF in routine clinical practice. A retrospective case study of 134 consecutive patients (alive at the time of analysis) with stable CHF, attending our heart failure clinic between 2002 and 2004, was conducted. Serum creatinine and haemoglobin levels checked …
Inhibitors of Tubulin Assembly Identified through Screening a Compound Library

Tubulin is the proposed target for drugs against cancer and helminths and is also a validated target in kinetoplastid parasites. With the aim of identifying new lead compounds against Leishmania sp. , tubulin isolated from L. tarentolae was used to screen a 10 000 compound library. One compound, Chembridge No. 7992831 (5), displayed an IC50 of 13 μm against Leishmania tubulin in an in vitro assembly assay and showed a greater than threefold selectivity over mammalian tubulin. Another compound, Chembridge No. 9067250 (8), exhibited good activity against mammalian tubulin (IC50 = 5.0 μm). This compound was also toxic to several cancer cell lines with IC50 values in the region of 1 μm. Subsequent testing of analogues of 8 contained within the library identified two compounds with greater potency against mammalian tubulin (IC50 values of 1.1 and 2.8 μm). The more potent antitubulin agent also showed promising activity against cancer cell lines in vitro, with IC50 values ranging from 0.18 to 0.73 μm.
The medial and lateral entorhinal cortex both contribute to contextual and item recognition memory: A test of the binding ofitems and context model

It has been suggested that the role of the hippocampus for episodic memory is to selectively bind together item and contextual information. One such model, the Binding of Items and Context (BIC) model, proposed that the perirhinal cortex provides item and the postrhinal/parahippocampal cortex provides context to the hippocampus via the medial (MEC) and lateral entorhinal cortices (LEC) to be bound into an episodic representation. This model proposes that item and context information are stored and processed independently and in parallel before hippocampal processing. To evaluate this model, the present experiment evaluated the role of the MEC and LEC for item and contextual novelty detection. The present results suggest that excitotoxic lesions to the LEC primarily disrupt item novelty detection, whereas lesions to the MEC primarily disrupt contextual novelty detection. These data provide a functional double dissociation between the MEC and LEC across item and contextual processing. Despite this dissociation, the present results suggest that item and contextual information are not represented independently before hippocampal processing. These data support the basic assumptions of the BIC model, but suggest that item and context information may interact in the entorhinal cortex. © 2013 Wiley Periodicals, Inc.
Mitotic Index Determined by Phosphohistone H3 Immunohistochemistry for Precise Grading in Follicular Lymphoma

The World Health Organization classification recommends follicular lymphoma (FL) grading (G1-3) by considering centroblast number, while also suggesting its influence on disease outcome. As centroblast counting and other proliferation markers have limitations, we looked for more specific measures of cellular activity in FL. Phosphorylated histone H3 (pHH3) was widely applied for the objective detection of mitotic activity in different tumors. The aim was to evaluate the utility of pHH3 protein in FL grading and compare its value with the classical features of cell proliferation. Representative samples from 48 FL patients and 9 samples with follicular hyperplasia were examined. Hematoxylin-eosin–based mitosis index (HE-MI), number of mitotic figures based on anti-pHH3 immunohistochemical staining (pHH3-MI), and percentage of Ki-67-positive cells [proliferation index (PI)] were determined and compared with centroblast-based histologic grade. PHH3-MI showed significant correlation with HE-MI (r=0.85, P<0.0001) and PI (r=0.84, P<0.0001). All 3 cell proliferation parameters showed significant correlation with histologic grade: HE-MI versus grade, r=0.85 (P<0.0001); PI versus grade, r=0.74 (P<0.0001); pHH3-MI versus grade, r=0.80 (P<0.0001). PHH3-MI showed continuous increase with the histologic grade. The pHH3-MI value was distinctive between the G2 and the G1 FL groups (P<0.0001) and was increased in G3 FL compared with that in the G2 FL group (P=0.0020). In conclusion, easy-to-perform mitotic counting following phosphohistone H3 immunohistochemistry (pHH3-MI) correlates well with centroblast-based grading. PHH3 immunohistochemistry offers a reliable quantification tool supporting lymphoma grading and can be recommended as an additional parameter for the precise subcategorization of FL cases.
Methods for Computer‐Aided Chemical Biology. Part 5: Rationalizing the Selectivity of Cathepsin Inhibitors on the Basis of Molecular Fragments and Topological Feature Distributions

We report a fragment‐based approach to analyze the target selectivity of active compounds. Sets of inhibitors were studied having different activity and selectivity for cathepsins, a family of therapeutically relevant thiol proteases. A systematic analysis was carried out of molecular fragments and atom environment features and their frequency of occurrence for compounds with different selectivity. Fragments extracted from target‐selective compounds and independently derived topological features were matched and selectivity markers were identified. Because there is only little overlap between selectivity and other compound set markers, combinations of selectivity set markers could be utilized to predict the selectivity of new cathepsin inhibitors.
International Journal of Parallel, Emergent and Distributed Systems

A common constraint in distributed data is that the database cannot be moved to other network sites due to computational costs, data size, or privacy considerations. All of the existing distributed algorithms for computing k -nearest neighbours ( k -NNs) are designed for horizontally partitioned or special case of vertically partitioned data where different sites contain different attributes for a common set of entities. In this article, we present a framework including a general model and a decomposable algorithm for computing k -NN in d -dimensional space across horizontally and vertically partitioned data in the most general situation in which existing distributed databases want to cooperate for k -NN. The key is to obtain valid results, with a minimum information disclosure. The proposed algorithm preserves the privacy of the data at individual sites by requiring transmission of only minimal information to other sites. The computation is performed by exchanging minimum number of higher level summaries so that even if they are captured by an intruder to actual data tuples can ever be revealed.
Structure‐based Drug Metabolism Predictions for Drug Design

Significant progress has been made in structure‐based drug design by pharmaceutical companies at different stages of drug discovery such as identifying new hits, enhancing molecule binding affinity in hit‐to‐lead, and reducing toxicities in lead optimization. Drug metabolism is a major consideration for modifying drug clearance and also a primary source for drug metabolite‐induced toxicity. With major cytochrome P450 structures identified and characterized recently, structure‐based drug metabolism prediction becomes increasingly attractive. In silico methods based on molecular and quantum mechanics such as docking, molecular dynamics and ab initio chemical reactivity calculations bring us closer to understand drug metabolism and predict drug–drug interactions. In this study, we review important progress in drug metabolism and common in silico techniques adopted to predict drug regioselectivity, stereoselectivity, reactive metabolites, induction, inhibition and mechanism‐based inactivation, as well as their implementation in hit‐to‐lead drug discovery.
FMSLPP: fake-message based sink location privacy preservation for WSNs against global eavesdroppers

Abstract Traditional encryption and authentication methods are not effective in preserving sink’s location privacy from a global adversary that could be monitoring the network’s traffic and time-of-arrival of traffic flows. In this paper, we present a novel method named fake-message based sink location privacy preservation (FMSLPP) to protect sink’s location privacy against global eavesdroppers. In this method, we let sensors generate fake messages with a probability before the sink sends a message, in order to confuse an adversary about the sink’s location. We also make each node have approximately the same traffic volume to protect the sink’s location privacy. Simulation results from two approaches of sensor deployment (random deployment or controlled deployment) indicate that FMSLPP makes it very difficult for the global adversary to identify the location of the sink; at the same time, transmission of fake messages does not impact significantly the network’s performance in terms of network life. Graphical Abstract Our protocol’s principle
ANI inactivation: Unconditioned anxiolytic effects of anisomycin in the ventral hippocampus

Although hippocampal function is typically described in terms of memory, recent evidence suggests a differentiation along its dorsal/ventral axis, with dorsal regions serving memory and ventral regions serving emotion. While long‐term memory is thought to be dependent on de novo protein synthesis because it is blocked by translational inhibitors such as anisomycin (ANI), online (moment‐to‐moment) functions of the hippocampus (such as unconditioned emotional responding) should not be sensitive to such manipulations since they are unlikely to involve neuroplasticity. However, ANI has recently been shown to suppress neural activity which suggests (1) that protein synthesis is critical for neural function and (2) that paradigms using ANI are confounded by its inactivating effects. We tested this idea using a neurobehavioral assay which compared the influence of intrahippocampal infusions of ANI at dorsal and ventral sites on unconditioned emotional behavior of rats. We show that ANI infusions in ventral, but not dorsal, hippocampus produced a suppression of anxiety‐related responses in two well‐established rodent tests: the elevated plus maze and shock‐probe burying tests. These results are similar to those previously observed when ventral hippocampal activity is directly suppressed (e.g., by using sodium channel blockers). The present study offers compelling behavioral evidence for the proposal that ANI adversely affects ongoing neural function and therefore its influence is not simply limited to impairing the consolidation of long‐term memories. © 2014 Wiley Periodicals, Inc.
Electroconvulsive stimulation, but not chronic restraint stress, causes structural alterations in adult rat hippocampus—A stereological study

The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress induces depression‐like behavior, without significantly changing neurogenesis, the total number of neurons or the volume of the hippocampus. Further, electroconvulsive stimulation prevents stress‐induced depression‐like behavior and increases neurogenesis. The total number of neurons and the granule cell layer volume was not affected by electroconvulsive stimulation. © 2014 Wiley Periodicals, Inc.
Functional connectivity of hippocampal and prefrontal networks during episodic and spatial memory based on real‐world environments

Several recent studies have compared episodic and spatial memory in neuroimaging paradigms in order to understand better the contribution of the hippocampus to each of these tasks. In the present study, we build on previous findings showing common neural activation in default network areas during episodic and spatial memory tasks based on familiar, real‐world environments (Hirshhorn et al. (2012) Neuropsychologia 50:3094–3106). Following previous demonstrations of the presence of functionally connected sub‐networks within the default network, we performed seed‐based functional connectivity analyses to determine how, depending on the task, the hippocampus and prefrontal cortex differentially couple with one another and with distinct whole‐brain networks. We found evidence for a medial prefrontal‐parietal network and a medial temporal lobe network, which were functionally connected to the prefrontal and hippocampal seeds, respectively, regardless of the nature of the memory task. However, these two networks were functionally connected with one another during the episodic memory task, but not during spatial memory tasks. Replicating previous reports of fractionation of the default network into stable sub‐networks, this study also shows how these sub‐networks may flexibly couple and uncouple with one another based on task demands. These findings support the hypothesis that episodic memory and spatial memory share a common medial temporal lobe‐based neural substrate, with episodic memory recruiting additional prefrontal sub‐networks. © 2014 Wiley Periodicals, Inc.