Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study.

RATIONALE Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood. OBJECTIVES We assessed the effect of exposure to traffic-related air pollution over 35 years on the incidence of COPD in a prospective cohort study. METHODS We followed 57,053 participants in the Danish Diet, Cancer, and Health cohort in the Hospital Discharge Register for their first hospital admission for COPD between 1993 and 2006. We estimated the annual mean levels of nitrogen dioxide (NO₂) and nitrogen oxides (NO(x)) at all residential addresses of the cohort participants since 1971 to an event or 2006 and used indicators of traffic near the residential address at recruitment. We assessed the association between exposure to air pollution and COPD incidence by Cox regression analyses for the full cohort, and for participants with and without comorbid conditions, including asthma, diabetes, or cardiovascular disease. MEASUREMENTS AND MAIN RESULTS A first hospital admission for COPD was recorded for 1,786 (3.4%) of 52,799 eligible subjects between recruitment (1993-1997) and 2006. COPD incidence was associated with the 35-year mean NO₂ level (hazard ratio, 1.08; 95% confidence interval, 1.02-1.14, per interquartile range of 5.8 μg/m³), with stronger associations in subjects with diabetes (1.29; 1.05-1.50) and asthma (1.19; 1.03-1.38). CONCLUSIONS Long-term exposure to traffic-related air pollution may contribute to the development of COPD with possibly enhanced susceptibility in people with diabetes and asthma.
Dural Venous Sinus Diameters in Children with Sickle Cell Disease: Correlation with History of Stroke in a Case–Control Study

Objectives The purpose of this study was to compare the diameters of the dural venous sinuses (DVSs) in children with sickle cell disease (SCD) with healthy controls and determine whether the size has any correlation to history of cerebral infarct among children with SCD. Methods A retrospective review compared demographics, medical history and magnetic resonance venography (MRV) findings in children with SCD with those in controls. Venous sinus diameters were measured on MRV in all subjects by the authors, who were blinded to the children’s clinical history. The study cohort included 38 MRVs in children with SCD and 38 control subjects. Results Statistical comparison showed children with SCD had significantly (P < 0.05) larger DVS diameters than controls. Among children with SCD with a history of stroke or silent infarct, DVS diameters were not significantly different. Conclusions Children with SCD had larger DVS diameters than did controls, regardless of the former group’s history of cerebral infarct. The difference in size of venous sinuses is important to be aware of during the interpretation of neuroimaging studies to avoid unneeded additional imaging or referral.
Circular RNA: an emerging key player in RNA world

Insights into the circular RNA (circRNA) exploration have revealed that they are abundant in eukaryotic transcriptomes. Diverse genomic regions can generate different types of RNA circles, implying their diversity. Covalently closed loop structures elevate the stability of this new type of noncoding RNA. High-throughput sequencing analyses suggest that circRNAs exhibit tissue- and developmental-specific expression, indicating that they may play crucial roles in multiple cellular processes. Strikingly, several circRNAs could function as microRNA sponges and regulate gene transcription, highlighting a new class of important regulators. Here, we review the recent advances in knowledge of endogenous circRNA biogenesis, properties and functions. We further discuss the current findings about circRNAs in human diseases. In plants, the roles of circRNAs remain a mystery. Online resources and bioinformatics identification of circRNAs are essential for the analysis of circRNA biology, although different strategies yield divergent results. The understanding of circRNA functions remains limited; however, circRNAs are enriching the RNA world, acting as an emerging key player.
Age‐related small vessel disease: a potential contributor to neurodegeneration in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system wherein, after an initial phase of transient neurological defects, slow neurological deterioration due to progressive neuronal loss ensues. Age is a major determinant of MS progression onset and disability. Over the past years, several mechanisms have been proposed to explain the key drivers of neurodegeneration and disability accumulation in MS. However, the effect of commonly encountered age‐related cerebral vessel disease, namely small vessel disease (SVD), has been largely neglected and constitutes the aim of this review. SVD shares some features with MS, that is, white matter demyelination and brain atrophy, and has been shown to contribute to the neuronal damage seen in vascular cognitive impairment. Several lines of evidence suggest that an interaction between MS and SVD may influence MS‐related neurodegeneration. SVD may contribute to hypoperfusion, reduced vascular reactivity and tissue hypoxia, features seen in MS. Venule and endothelium abnormalities have been documented in MS but the role of arterioles and of other neurovascular unit structures, such as the pericyte, has not been explored. Vascular risk factors (VRF) have recently been associated with faster progression in MS, though the mechanisms are unclear since very few studies have addressed the impact of VRF and SVD on MS imaging and pathology outcomes. Therapeutic agents targeting the microvasculature and the neurovascular unit may impact both SVD and MS and may benefit patients with dual pathology.
Ensemble Based Real-Time Adaptive Classification System for Intelligent Sensing Machine Diagnostics

The deployment of a sensor node to manage a group of sensors and collate their readings for system health monitoring is gaining popularity within the manufacturing industry. Such a sensor node is able to perform real-time configurations of the individual sensors that are attached to it. Sensors are capable of acquiring data at different sampling frequencies based on the sensing requirements. The different sampling rates affect power consumption, sensor lifespan, and the resultant network bandwidth usage due to the data transfer incurred. These settings also have an immediate impact on the accuracy of the diagnostics and prognostics models that are employed for system health monitoring. In this paper, we propose a novel adaptive classification system architecture for system health monitoring that is well suited to accommodate and take advantage of the variable sampling rate of sensors. As such, our proposed system is able to yield a more effective health monitoring system by reducing the power consumption of the sensors, extending the sensors' lifespan, as well as reducing the resultant network traffic and data logging requirements. We also propose an ensemble based learning method to integrate multiple existing classifiers with different feature representations, which can achieve significantly better, stable results compared with the individual state-of-the-art techniques, especially in the scenario when we have very limited training data. This result is extremely important in many real-world applications because it is often impractical, if not impossible, to hand-label large amounts of training data.
Photoperiodic Programming of the SCN and Its Role in Photoperiodic Output

Though the seasonal response of organisms to changing day lengths is a phenomenon that has been scientifically reported for nearly a century, significant questions remain about how photoperiod is encoded and effected neurobiologically. In mammals, early work identified the master circadian clock, the suprachiasmatic nuclei (SCN), as a tentative encoder of photoperiodic information. Here, we provide an overview of research on the SCN as a coordinator of photoperiodic responses, the intercellular coupling changes that accompany that coordination, as well as the SCN's role in a putative brain network controlling photoperiodic input and output. Lastly, we discuss the importance of photoperiodic research in the context of tangible benefits to human health that have been realized through this research as well as challenges that remain.
Modelling and analysis of differential VCOs

We present a systematic non‐linear analysis of differential voltage controlled oscillators (VCOs), both bipolar and MOS. Using the standard device models, we derive the second‐order non‐linear equation describing the behaviour of these oscillators, which is formulated in a perturbation form. The solution of this equation is obtained as a particular case of the solution of the most general equation of second‐order oscillators, which is solved through a suitable perturbation method. Unlike a pure numerical analysis, simple analytical relationships are derived for predicting the steady‐state oscillation, its transient behaviour and for ascertaining the existence of a stable oscillation in differential VCOs. These relationships, leading to results which well agree with the SPICE simulations, are useful in both analysis and design. Copyright © 2004 John Wiley & Sons, Ltd.
Financial Distress Prediction: Empirical Evidence From Indian Automobile Companies

Financial distress is of crucial importance in financial management especially in the case of competitive environment. Failure is not an impulsive outcome and it grows constantly in stages. A spontaneous protective effort could be accommodated if the company is anticipated to be proceeding in the direction of potential bankruptcy and this can help alleviate the financial distress to all investor and decrease the costs of bankruptcy. This study extends a failure prediction model for Indian Automobile companies. This study hopes to accommodate some important results relevant to authorities and stake holders. The capability to detect potential financial problems at a premature stage is absolutely essential because it helps to ensure business, financial, economic and political environment stability. The results show good performance with a highly correct categorization factuality rate of more than 90%. Eight ratios were determined significant out of 38 financial ratios utilized in this analysis to discriminate among failed and non- failed companies. The significant variables are Operating margin (%), Gross profit margin (%), Return on long term funds (%), Total debt/equity, Cash earnings retention ratio, Exports as percent of total sales, Import companies in raw material consumed, Bonus component in equity capital (%).
Development of Potent Inhibitors of Receptor Tyrosine Kinases by Ligand-Based Drug Design and Target-Biased Phenotypic Screening

Pyrazolopyrimidines with potent antiproliferative properties were developed by an adaptive strategy that applies ligand-based design and phenotypic screening iteratively and is informed by biochemical assays. To drive development toward specific oncopathways, compounds were tested against cancer cells that overexpress, or not, AXL kinase. Identified phenotypic hits were found to inhibit oncotargets AXL, RET, and FLT3. Subsequent optimization generated antiproliferative lead compounds with unique selectivity profiles, including selective AXL inhibitors and a highly potent inhibitor of FLT3.
Identification of monosodium urate crystal deposits in patients with asymptomatic hyperuricemia using dual-energy CT

Objectives Dual-energy CT (DECT) scan is a sensitive and specific tool used to visualise and quantify monosodium urate (MSU) crystal deposits in the joints. Few studies have examined MSU crystal deposits in patients with asymptomatic hyperuricemia (ie, hyperuricemia in the absence of gout) using DECT. Methods We conducted a prospective, non-interventional cross-sectional study to detect MSU crystal deposits on DECT scans among patients with asymptomatic hyperuricemia. We also examined patient factors associated with subclinical MSU crystal deposits. Out of 130 subjects aged ≥40 years with metabolic syndrome screened for serum uric acid (sUA) levels ≥6.5 mg/dL, 46 underwent a foot/ankle DECT scan. Results The mean age of the study participants was 62 (±8) years, 41% were men and the mean sUA level was 7.8 (±1.0) mg/dL. Seven (15%) of 46 patients had MSU crystal deposits on DECT with a mean total volume of 0.13 (±0.14) cm3. In the univariable logistic regression analysis, older age had a significant association with presence of MSU crystal deposits (OR 1.20, 95% CI 1.03 to 1.39), but sUA did not (OR 1.36, 95% CI 0.63 to 2.95). In the univariable analysis, sUA levels showed a trend towards a modest linear association (β=0.11, P=0.09) with total volume of MSU crystal deposits. Conclusions Fifteen per cent of patients with asymptomatic hyperuricemia had subclinical MSU crystal deposits on foot/ankle DECT scans. Older age, but not sUA, was significantly associated with presence of subclinical MSU crystal deposits among patients with asymptomatic hyperuricemia. Clinical significance of these subclinical MSU crystal deposits needs to be determined.
Arsenic‐Mediated Activation of the Nrf2‐Keap1 Antioxidant Pathway

Arsenic is present in the environment and has become a worldwide health concern due to its toxicity and carcinogenicity. However, the specific mechanism(s) by which arsenic elicits its toxic effects has yet to be fully elucidated. The transcription factor nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) has been recognized as the master regulator of a cellular defense mechanism against toxic insults. This review highlights studies demonstrating that arsenic activates the Nrf2‐Keap1 antioxidant pathway by a distinct mechanism from that of natural compounds such as sulforaphane (SF) found in broccoli sprouts or tert‐butylhyrdoquinone (tBHQ), a natural antioxidant commonly used as a food preservative. Evidence also suggests that arsenic prolongs Nrf2 activation and may mimic constitutive activation of Nrf2, which has been found in several human cancers due to disruption of the Nrf2‐Keap1 axis. The current literature strongly suggests that activation of Nrf2 by arsenic potentially contributes to, rather than protects against, arsenic toxicity and carcinogenicity. The mechanism(s) by which known Nrf2 activators, such as the natural chemopreventive compounds SF and lipoic acid, protect against the deleterious effects caused by arsenic will also be discussed. These findings will provide insight to further understand how arsenic promotes a prolonged Nrf2 response, which will lead to the identification of novel molecular markers and development of rational therapies for the prevention or intervention of arsenic‐induced diseases.
An Edge Computing Empowered Radio Access Network with UAV-Mounted FSO Fronthaul and Backhaul: Key Challenges and Approaches

One promising approach to address the supply- demand mismatch between the terrestrial infrastructure and temporary and/or unexpected traffic demands is to leverage the UAV technologies. Motivated by the recent advancement of UAV technologies and retromodulator-based free space optical communication, we propose a novel edge-computing-empowered radio access network architecture where the fronthaul and backhaul links are mounted on UAVs for rapid event response and flexible deployment. The implementation of hardware and networking technologies for the proposed architecture are investigated. Due to the limited payload and endurance as well as the high mobility of UAVs, research challenges related to communication resource management and recent research progress are reported.
Fermented Wheat Germ Extract Inhibits Glycolysis/Pentose Cycle Enzymes and Induces Apoptosis through Poly(ADP-ribose) Polymerase Activation in Jurkat T-cell Leukemia Tumor Cells*

The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC50 concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G1 peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodide- and annexin V-stained cells indicated that the growth-inhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased13C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC50 (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects.
The Interactive Narrator Tool: Effective Requirements Exploration and Discussion through Visualization

Requirements visualization can contribute to requirements comprehension through the creation of conceptual models. However, these models can become hard to read and current tool support is minimal. Applying the right visualization mechanisms can help construct models that are more readable. To such extent, we present the Interactive Narrator tool: a web application that helps practitioners analyze software requirements at an abstract level. Interactive Narrator uses Natural Language Processing to derive conceptual models from user stories, which are then translated into an interactive network diagram with zooming and filtering capabilities. Interactive Narrator facilitates discussion and aims to accelerate the understanding of large sets of software requirements.
Point of View Commentary on "Preoperative Chronic Opioid Therapy: a Risk Factor for Complications, Readmission, Continued Opioid Use and Increased Costs After One- and Two-level Posterior Lumbar Fusion".

he epidemic of opioid use in the United States is daily These findings support recommendations for minimizing news. This includes growing attention to judicious T opioid prescribing following surgical interventions. Some research has focused on surgery for nonpainful conditions such as thyroid disease or cataracts. Issues surrounding surgery for chronic painful conditions, like back pain, are more complex because many patients use long term preoperative opioids. Spine surgery, in particular, often involves patients using long-term preoperative opioids, which strongly predicts continued postoperative use. Preoperative opioid use is also associated with longer or worse surgical site pain, hospital stay, return to work, surgical complications, and functional outcomes. Surgical patients in general often receive excessively large postoperative opioid prescriptions, beyond amounts needed for analgesia. The study by Jain et al strengthens several of these observations on users of preoperative opioids, adding new information on older populations and on increased use of emergency visits, rehospitalization, reoperation, and subsequent injections. The study used commercial insurance claims, and could miss utilization if patients changed or lost insurance, or paid for medications out of pocket. Nonetheless, it used an enormous database, careful definitions and case selection, and a thorough analysis.
CrossTalk proposal: Proton permeation through HV1 requires transient protonation of a conserved aspartate in the S1 transmembrane helix

Here I present evidence in support of the premise that H+ selective permeation through the voltage gated proton channel HV1 involves obligatory protonation/deprotonation of an aspartic acid residue (Asp in human HV1) in the middle of the S1 transmembrane helix. An alternative view is the ‘frozen water’ mechanism, in which the channel traps one or more water molecules that block cation flux but permit Grotthuss-style proton hopping. I concede at the outset that the issue is not resolved and is not in fact resolvable based on current evidence. The historical basis for evaluating HV1 conduction mechanisms was a series of measurements of the biophysical properties of H+ currents. For over a decade the fundamental paradigm was to compare proton fluxes through HV1 with those through gramicidin (Table 1), known to be a cylindrical pore through which ions and water permeate in single file (Rosenberg & Finkelstein, 1978; Wallace & Ravikumar, 1988). The characteristics of H+ current through gramicidin differ from proton conduction in bulk water, but H+ conduction through HV1 is radically different from both (Table 1). Hence, many papers from this era concluded that the pathway through HV1 is more complex than a water-filled pore and includes obligatory protonation/deprotonation of at least one amino acid side-chain (DeCoursey & Cherny, 1994, 1997, 1998).
Importance of parasites and their life cycle characteristics in determining the structure of a large marine food web

Summary 1Despite their documented effects on trophic interactions and community structure, parasites are rarely included in food web analyses. The transmission routes of most parasitic helminths follow closely the trophic relationships among their successive hosts and are thus embedded in food webs, in a way that may influence energy flow and the structure of the web. 2We investigated the impact of parasitism on the food web structure of a New Zealand intertidal mudflat community. Different versions of the food web were analysed, one with no parasites, one with all parasite species and several other versions, each including a single parasite species. We measured key food web metrics such as food chain length, linkage density and proportions of top, intermediate and basal species. 3The inclusion of all parasite species in the food web resulted in greatly increased mean and maximum food chain length, but had little impact on linkage density and realized connectance. The main change caused by introduction of parasites was the relegation of a number of species from top predators to intermediate status, although the addition of parasites as top predators left the actual ratio of predators to prey relatively unchanged. 4When individual parasites were added to the food web, their effect on food web properties was generally minimal. However, one trematode species that affected several host species, because of its complex life cycle and low host specificity, produced food web properties similar to those in the web version including all parasite species. 5The respective effect of individual parasite species was roughly proportional to the number of host species they affected, and thus the life cycle characteristics of parasites determine to a large extent their impact on food web structure. The next step would be to quantify how they affect energy flow through the web.