Miracle-dz/UniFAR-FTUs huggingface dataset:
Aplastic Anemia Rescued by Exhaustion of Cytokine-secreting CD8+ T Cells in Persistent Infection with Lymphocytic Choriomeningitis Virus

Aplastic anemia may be associated with persistent viral infections that result from failure of the immune system to control virus. To evaluate the effects on hematopoiesis exerted by sustained viral replication in the presence of activated T cells, blood values and bone marrow (BM) function were analyzed in chronic infection with lymphocytic choriomeningitis virus (LCMV) in perforin-deficient (P0/0) mice. These mice exhibit a vigorous T cell response, but are unable to eliminate the virus. Within 14 d after infection, a progressive pancytopenia developed that eventually was lethal due to agranulocytosis and thrombocytopenia correlating with an increasing loss of morphologically differentiated, pluripotent, and committed progenitors in the BM. This hematopoietic disease caused by a noncytopathic chronic virus infection was prevented by depletion of CD8+, but not of CD4+, T cells and accelerated by increasing the frequency of LCMV-specific CD8+ T cells in T cell receptor (TCR) transgenic (tg) mice. LCMV and CD8+ T cells were found only transiently in the BM of infected wild-type mice. In contrast, increased numbers of CD8+ T cells and LCMV persisted at high levels in antigen-presenting cells of infected P0/0 and P0/0 × TCR tg mice. No cognate interaction between the TCR and hematopoietic progenitors presenting either LCMV-derived or self-antigens on the major histocompatibility complex was found, but damage to hematopoiesis was due to excessive secretion and action of tumor necrosis factor (TNF)/lymphotoxin (LT)-α and interferon (IFN)-γ produced by CD8+ T cells. This was studied in double-knockout mice that were genetically deficient in perforin and TNF receptor type 1. Compared with P0/0 mice, these mice had identical T cell compartments and T cell responses to LCMV, yet they survived LCMV infection and became life-long virus carriers. The numbers of hematopoietic precursors in the BM were increased compared with P0/0 mice after LCMV infection, although transient blood disease was still noticed. This residual disease activity was found to depend on IFN-γ–producing LCMV-specific T cells and the time point of hematopoietic recovery paralleled disappearance of these virus-specific, IFN-γ–producing CD8+ T cells. Thus, in the absence of IFN-γ and/or TNF/LT-α, exhaustion of virus-specific T cells was not hampered.
Classification of crypto-coins and tokens from the dynamics of their power law capitalisation distributions

We empirically verify that the market capitalisations of coins and tokens in the cryptocurrency universe follow power law distributions with significantly different values, with the tail exponent falling between 0.5 and 0.7 for coins, and between 1.0 and 1.3 for tokens. We provide a rational for this, based on a simple birth-proportional growth-death model previously introduced to describe firms, cities, webpages, etc. We validate the model and its main predictions, in terms of proportional growth and linear versus square-root growth law of the mean and standard deviation of market capitalisation as a function of time interval. Estimating the main parameters of the model, the theoretical predictions for the power law exponents of coins and tokens distribution are in remarkable agreement with the empirical estimations, given the simplicity of the model in the face of the complexity and non-stationarity of the crypto-currency world. Our results clearly characterizes coins as being "entrenched incumbents" and tokens as an "explosive immature ecosystem", largely due to massive and exuberant Initial Coin Offering activity in the token space. The theory predicts that the exponent for tokens should converge to 1 in the future, reflecting a more reasonable rate of new entrants associated with genuine technological innovations.
Heritability of Hemodynamic Reactivity to Laboratory Stressors in a Homogenous Arab Population: ‘Oman Family Study’

Abstract Background: Exaggerated cardiovascular reactivity to stressful stimuli may be a risk factor for the development of hypertension. The genetic influence on blood pressure (BP) reactivity to stress and its control mechanisms has been receiving considerable support. This study aims at examining the heritability of BP and its intermediate hemodynamic phenotypes to acute stress in a homogeneous Arab population. Methods: Parameters were computed from continuous BP, electrocardiography and impedance cardiography measurements, during rest, word conflict (WCT) and cold pressor (CPT) tests. Heritability estimates (h2) were obtained using the variance components-based approach implemented in the SOLAR software package. Results: Reactivity scores for WCT and CPT increased significantly (P < .05) for systolic (SBP), diastolic (DBP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR). They decreased significantly (P < .05) for stroke volume (SV), left ventricular ejection time (LVET), end diastolic (EDI) and cardiac contractility (IC) indices. Univariate analysis detected heritability estimates that ranged from 0.19–0.35 for rest, 0.002–0.40 for WCT and 0.08–0.35 for CPT. Conclusion: In this unique cohort, resting as well as challenged cardiovascular phenotypes are significantly influenced by additive genetic effects. Heritability estimates for resting phenotypes are in a relatively narrow range, while h2 for their reactivity is somewhat broader with lower estimates. Further analyses of this study may offer important opportunities for gene finding in hypertension. What is Known About the Topic: (1) cardiovascular reactivity to stress predicts cardiovascular disease; (2) genetic susceptibility plays an important role in stress reactivity. Family studies using the cold pressure test reported significant heritability for blood pressure. What this Study Adds: (1) this cohort is from five highly consanguineous isolated Arab pedigrees with genetically verified genealogical records and environmental homogeneity; (2) This is the first study to estimate heritability of detailed intermediate hemodynamic phenotypes that make up normal blood pressure.
Portable Brain-Computer Interface for the Intensive Care Unit Patient Communication Using Subject-Dependent SSVEP Identification

A major predicament for Intensive Care Unit (ICU) patients is inconsistent and ineffective communication means. Patients rated most communication sessions as difficult and unsuccessful. This, in turn, can cause distress, unrecognized pain, anxiety, and fear. As such, we designed a portable BCI system for ICU communications (BCI4ICU) optimized to operate effectively in an ICU environment. The system utilizes a wearable EEG cap coupled with an Android app designed on a mobile device that serves as visual stimuli and data processing module. Furthermore, to overcome the challenges that BCI systems face today in real-world scenarios, we propose a novel subject-specific Gaussian Mixture Model- (GMM-) based training and adaptation algorithm. First, we incorporate subject-specific information in the training phase of the SSVEP identification model using GMM-based training and adaptation. We evaluate subject-specific models against other subjects. Subsequently, from the GMM discriminative scores, we generate the transformed vectors, which are passed to our predictive model. Finally, the adapted mixture mean scores of the subject-specific GMMs are utilized to generate the high-dimensional supervectors. Our experimental results demonstrate that the proposed system achieved 98.7% average identification accuracy, which is promising in order to provide effective and consistent communication for patients in the intensive care.
Traumatic injury to peripheral nerves

This article reviews the epidemiology and classification of traumatic peripheral nerve injuries, the effects of these injuries on nerve and muscle, and how electrodiagnosis is used to help classify the injury. Mechanisms of recovery are also reviewed. Motor and sensory nerve conduction studies, needle electromyography, and other electrophysiological methods are particularly useful for localizing peripheral nerve injuries, detecting and quantifying the degree of axon loss, and contributing toward treatment decisions as well as prognostication. © 2000 American Association of Electrodiagnostic Medicine. Published by John Wiley & Sons, Inc. Muscle Nerve 23: 863–873, 2000
Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia: Two-Year Follow-up in the HypoCOMPaSS Randomized Clinical Trial

OBJECTIVE Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care. RESEARCH DESIGN AND METHODS Ninety-six adults with type 1 diabetes (29 ± 12 years’ duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness. RESULTS Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P < 0.0001). Severe hypoglycemia rate was reduced from 8.9 ± 12.8 episodes/person-year over the 12 months prestudy to 0.4 ± 0.8 over 24 months (P < 0.0001). HbA1c improved (baseline 8.2 ± 3.2% [66 ± 12 mmol/mol] vs. 24 months 7.7 ± 3.1% [61 ± 10 mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of hypoglycemia were sustained. There were no significant differences between interventions at 24 months. CONCLUSIONS Optimized insulin replacement and glucose monitoring underpinned by hypoglycemia-focused structured education should be provided to all with type 1 diabetes complicated by impaired awareness of hypoglycemia.
Progress on the adjacent vertex distinguishing edge colouring conjecture

A proper edge colouring of a graph is adjacent vertex distinguishing if no two adjacent vertices see the same set of colours. Using a clever application of the Local Lemma, Hatami (2005) proved that every graph with maximum degree $\Delta$ and no isolated edge has an adjacent vertex distinguishing edge colouring with $\Delta + 300$ colours, provided $\Delta$ is large enough. We show that this bound can be reduced to $\Delta + 19$. This is motivated by the conjecture of Zhang, Liu, and Wang (2002) that $\Delta + 2$ colours are enough for $\Delta \geq 3$.
A Case Study on the Implementation of a Positive Youth Development Program (Project P.A.T.H.S.) in Hong Kong: Learning from the Experimental Implementation Phase

This investigation of the implementation of a positive youth development program (Project P.A.T.H.S.) was part of a large study undertaken comprehensively to explore how effective the Tier 1 Program was in practice and how the results can shed light on future developments. Utilizing a case study approach, individual and focus group interviews were conducted in 2007 to examine the factors that influence the process and quality of implementation of the Tier 1 Program of the Project P.A. T.H. S. The focus of this study was on how the implementers of a school made use of the experience gained in the Experimental Implementation Phase (EIP) in 2005/06 to improve the program implementation quality in the Full Implementation Phase (FIP) in 2006/07. Results showed that the program implementation in the FIP was generally high and the program was well received by the implementers. Factors that facilitated the implementation of the program were identified, including the adoption of an incremental change strategy, the incorporation of the program into both formal and informal curricula, positive perceptions of the program among staff and agency social workers, sufficient school administrative support, excellent cooperation between the school and the social work agency, presence of a dedicated school contact person and instructors who engaged themselves in continuous quality improvement of the implementation, and an emphasis on application of what had been learned. Difficulties encountered by the school in the process of implementation were also observed. Based on the present findings, key process variables that facilitate or impede the implementation of positive youth development programs are discussed. Implications for future program implementation are also discussed.
Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues.

BACKGROUND & AIMS Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.
Stimulating the Healthy Brain to Investigate Neural Correlates of Motor Preparation: A Systematic Review

Objective Noninvasive brain stimulation techniques can be used to selectively increase or decrease the excitability of a cortical region, providing a unique opportunity to assess the causal contribution of that region to the process being assessed. The objective of this paper is to systematically examine studies investigating changes in reaction time induced by noninvasive brain stimulation in healthy participants during movement preparation. Methods A systematic review of the literature was performed in the PubMed, MEDLINE, EMBASE, PsycINFO, and Web of science databases. A combination of keywords related to motor preparation, associated behavioral outcomes, and noninvasive brain stimulation methods was used. Results Twenty-seven studies were included, and systematic data extraction and quality assessment were performed. Reaction time results were transformed in standardised mean difference and graphically pooled in forest plots depending on the targeted cortical area and the type of stimulation. Conclusions Despite methodological heterogeneity among studies, results support a functional implication of five cortical regions (dorsolateral prefrontal cortex, posterior parietal cortex, supplementary motor area, dorsal premotor cortex, and primary motor cortex), integrated into a frontoparietal network, in various components of motor preparation ranging from attentional to motor aspects.
Codecast: Supporting Data Driven In-Network Processing for Low-Power Wireless Sensor Networks

This paper presents Codecast, a many-to-many communication protocol for low-power sensor networks that provide high throughput and reliable data sharing from multiple sources to multiple destinations of a network. Codecast uses physical layer capture on concurrent transmissions for high spatial reuse and a network-assisted network coding for high throughput as the core techniques. Our extensive evaluation in two large-scale testbed deployments (Indriya and Flocklab) shows that Codecast provides up to 4x the throughput of Chaos and 1.8x the throughput of LWB for many-to-many data communication. Finally, we demonstrate the utility of Codecast through a distributed channel selection mechanism and a link state based routing protocol.
Combination of anginex gene therapy and radiation decelerates the growth and pulmonary metastasis of human osteosarcoma xenografts

Investigate whether rAAV‐anginex gene therapy combined with radiotherapy could decrease growth and pulmonary metastasis of osteosarcoma in mice and examine the mechanisms involved in this therapeutic strategy. During in vitro experiment, multiple treatment regimes (rAAV‐eGFP, radiotherapy, rAAV‐anginex, combination therapy) were applied to determine effects on proliferation of endothelial cells (ECs) and G‐292 osteosarcoma cells. During in vivo analysis, the same multiple treatment regimes were applied to osteosarcoma tumor‐bearing mice. Use microcomputed tomography to evaluate tumor size. Eight weeks after tumor cell inoculation, immunohistochemistry was used to assess the therapeutic efficacy according to microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and terminal‐deoxynucleotidyl transferase‐mediated nick‐end labeling (TUNEL) assays. Metastasis of lungs was also evaluated by measuring number of metastatic nodules and wet weight of metastases. The proliferation of ECs and the tumor volumes in combination therapy group were inhibited more effectively than the other three groups at end point (P < 0.05). Cell clone assay showed anginex had radiosensitization effect on ECs. Immunohistochemistry showed tumors from mice treated with combination therapy exhibited the lowest MVD and proliferation rate, with highest apoptosis rate, as confirmed by IHC staining for CD34 and PCNA and TUNEL assays (P < 0.05). Combination therapy also induced the fewest metastatic nodules and lowest wet weights of the lungs (P < 0.05). rAAV‐anginex combined with radiotherapy induced apoptosis of osteosarcoma cells and inhibited tumor growth and pulmonary metastasis on the experimental osteosarcoma models. We conclude that the primary mechanism of this process may be due to sensitizing effect of anginex to radiotherapy.
Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium nanoparticles with amantadine through ROS-mediated AKT signaling pathways

Introduction As a therapeutic antiviral agent, the clinical application of amantadine (AM) is limited by the emergence of drug-resistant viruses. To overcome the drug-resistant viruses and meet the growing demand of clinical diagnosis, the use of biological nanoparticles (NPs) has increased in order to develop novel anti-influenza drugs. The antiviral activity of selenium NPs with low toxicity and excellent activities has attracted increasing attention for biomedical intervention in recent years. Methods and results In the present study, surface decoration of selenium NPs by AM (Se@AM) was designed to reverse drug resistance caused by influenza virus infection. Se@ AM with less toxicity remarkably inhibited the ability of H1N1 influenza to infect host cells through suppression of the neuraminidase activity. Moreover, Se@AM could prevent H1N1 from infecting Madin Darby Canine Kidney cell line and causing cell apoptosis supported by DNA fragmentation and chromatin condensation. Furthermore, Se@AM obviously inhibited the generation of reactive oxygen species and activation of phosphorylation of AKT. Conclusion These results demonstrate that Se@AM is a potentially efficient antiviral pharmaceutical agent for H1N1 influenza virus.
An automated method to determine angular preferentiality using LFPs recorded from rat barrel cortex by brain-chip interface under mechanical whisker stimulation

The sensory information processing in the rodents is mainly done by whisking, through which they explore the environment, perform object localization, texture and shape discrimination very precisely. During whisking, microcircuits in the corresponding barrel columns get activated to segregate and integrate the tactile information through the information processing pathway. To primarily understand the whisking mechanism angular preferentiality determination is very important. In this work we propose an automated method to determine different events present in the local field potentials (LFPs), calculate latencies and amplitudes related to those events and use them along with the stimulation angle information to determine the angular preferentiality. The method is extensively tested on LFPs recorded from S1 barrel cortex of anesthetized rats using EOSFET (Electrolyte-Oxide-Semiconductor Field Effect Transistor) based neuronal probes.
Historie acetylation in reproductive organs: Significance of histone deacetylase inhibitors in gene transcription

Acetylation of histories is cooperatively regulated by two groups of enzymes, histone acetyltransferases and histone deacetylases. Histone acetylation status plays a fundamental role in the level of gene transcription; numerous studies have demonstrated that histone deacetylase inhibitors cause cell growth arrest, apoptosis, and differentiation in various cells including human mammary gland and endometrial cells by altering transcription of a small number of genes. A recent study has also shown that a highly acetylated histone status alters cell motility. After the present review of the published reports on the mechanisms underlying histone acetylation and in vitro effects of histone deacetylase inhibitors, we conclude that this class of agents may have potential not only as anticancer drugs, but also as inducers of differentiation and/or motility for benign gynecologic conditions such as endometriosis and disorders of endometrial differentiation and dysfunction.