Miracle-dz/UniFAR-FTUs huggingface dataset:
The Global Initiative for Asthma (GINA): 25 years later

The Global Initiative for Asthma (GINA) was launched in 1993 under the auspices of the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization to produce a global strategy on asthma management and prevention. Now constituted as a non-profit entity, it continues to produce, on an annual basis, the most widely cited evidence-based report on the optimal management of asthma in both adults and children intended for global use. Although the GINA Report is often viewed and used as an asthma treatment guideline, it is designed to be a clinically oriented strategy document that supports the development of practice guidelines in different countries and regions. Other GINA products, including the report's pocket guides, teaching slide kits and implementation tools, are also offered free of charge for public use. The GINA Scientific Committee comprises recognised international experts from primary, secondary and tertiary centres of care who are actively involved in both the care of patients and research in asthma. The GINA Assembly is a forum for exchange of scientific information and discussions on initiatives to improve asthma care in various countries, focusing on implementation strategies. GINA plays a role in shaping research on the diagnosis and treatment of asthma and informs the development of point of care practice guides and decision support tools. GINA supports the objectives of raising awareness of asthma and improving access to therapy and quality of care for asthmatic patients, in addition to presenting and promoting continuously updated evidence-based treatment approaches for global use. GINA, launched in 1993, produces an annual evidence-based report on the optimal management of asthma intended for global use, along with various resources, in addition to promoting initiatives to improve asthma care. bit.ly/2W3yDpU
A Survey on Object Tracking Algorithms

Object tracking in video processing is an emerging method to achieve variety of real time applications, like compression, video surveillance etc. Detection of moving objects in video streams is the first relevant step of information extraction in much computer vision application. In compressed domain video, object can be tracked based on motion vector. In this paper we present a survey of various objects tracking algorithm to estimate the efficiency of tracking.
DASC cache: dealing with cache access time and virtual indexing

In a microprocessor, the cache hit time generally determines the clock frequency. But for the ten last years, a technological trend is the increaseof the cache miss penalty in terms of instruction issue delays, then maintaining the cache miss ratio as low as possible is also of particular interest. For a few years, there has been numerous studies focusing on a low cache hit time while maintaining low cache miss ratio. Unfortunately most of the proposed solutions implicitly suppose that the cache is virtually indexed. When using virtually indexed caches, the operating system (or may be some specific hardware) has to manage the consistency of caches and memory. In this paper, we propose the Direct-mapped Access Set-associative Check cache (DASC) for addressing both difficulties. On a DASC cache, the cache array is direct-mapped then the cache hit time is low, but as the tag array is set-associative, the external miss ratio is the same as the miss ratio of a set- associative cache. When the size of an associativity degree of the tag array is tied to the minimum page size, a virtually indexed DASC cache correctly handles all difficulties associated with cache consistency. Trace driven simulations show that, for cache sizes in the range of 16-32 Kbytes and for current minimum page size in the range 4-8 Kbytes, using a DASC cache is a valuable trade-off because it allows fast cache hit time and low cache miss ratio while cache consistency management is performed by hardware.
Data as promise: Reconfiguring Danish public health through personalized medicine

‘Personalized medicine’ might sound like the very antithesis of population science and public health, with the individual taking the place of the population. However, in practice, personalized medicine generates heavy investments in the population sciences – particularly in data-sourcing initiatives. Intensified data sourcing implies new roles and responsibilities for patients and health professionals, who become responsible not only for data contributions, but also for responding to new uses of data in personalized prevention, drawing upon detailed mapping of risk distribution in the population. Although this population-based ‘personalization’ of prevention and treatment is said to be about making the health services ‘data-driven’, the policies and plans themselves use existing data and evidence in a very selective manner. It is as if data-driven decision-making is a promise for an unspecified future, not a demand on its planning in the present. I therefore suggest interrogating how ‘promissory data’ interact with ideas about accountability in public health policies, and also with the data initiatives that the promises bring about. Intensified data collection might not just be interesting for what it allows authorities to do and know, but also for how its promises of future evidence can be used to postpone action and sidestep uncomfortable knowledge in the present.
Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome.

When does an illness become a disease? When the underlying biological abnormalities that cause the symptoms and signs of the illness are clarified. The illness now called myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) was first described in the mid-1980s. At that time, nothing was known about its underlying biology. Indeed, because many standard laboratory test results were normal, some clinicians explained to patients that “there is nothing wrong. ” There was, of course, an alternative explanation: the standard laboratory tests might not have been the right tests to identify the underlying abnormalities. Over the past 35 years, thousands of studies from laboratories in many countries have documented underlying biological abnormalities involving many organ systems in patients with ME/CFS, compared with healthy controls: in short, there is something wrong. Moreover, most of the abnormalities are not detected by standard laboratory tests. In 2015, the Institute of Medicine of the National Academy of Sciences concluded that ME/ CFS “is a serious, chronic, complex systemic disease that often can profoundly affect the lives of patients,” affects up to an estimated 2.5 million people in the United States, and generates direct and indirect expenses of approximately $17 billion to $24 billion annually.1 Over the past several years, the National Institutes of Health (NIH) has expanded its research efforts directed toward this disease. It has initiated an unusually comprehensive multisystem study at the NIH Clinical Center, funded 3 extramural ME/CFS research centers and 1 data coordinating center, awarded supplemental support to 7 existing grants, and held regular telebriefings on the illness (as has the Centers for Disease Control and Prevention). 2 A 2-day conference at the NIH in April 2019 highlighted recent progress. New research was presented that both reinforced and expanded on previous reports. Equally important, several plausible models were proposed that could explain many of the abnormalities that have been described.
T-type Ca 2 + channel blocker mibefradil blocks ORAI channels via acting on extracellular surface

BACKGROUND AND PURPOSE Mibefradil (Mib), a T-type Ca 2+ channel blocker, has been investigated for treating solid tumours. However, its underlying mechanisms are still unclear. Here we aimed to investigate the pharmacological aspect of Mib on ORAI store-operated Ca 2+ channels. EXPERIMENTAL APPROACH Human ORAI1-3 in tetracycline-regulated pcDNA4/TO vectors was transfected into HEK293 T-REx cells with STIM1 stable expression. The ORAI currents were recorded by whole-cell and excised-membrane patch clamp. Ca 2+ influx or release was measured by Fura-PE3/AM. Cell growth and death were monitored by WST-1, LDH assays and flow cytometry. KEY RESULTS Mib inhibited ORAI1, ORAI2 and ORAI3 currents in a dose-dependent manner. The IC 50 for ORAI1, ORAI2 and ORAI3 was 52.6 μM, 14.1 μM and 3.8 μM, respectively. Outside-out patch demonstrated that perfusion of 10 μM Mib to the extracellular surface completely blocked ORAI3 currents and single channel activity evoked by 2-APB. Intracellular application of Mib did not alter ORAI3 channel activity. Mib at higher concentrations (>50 µM) inhibited Ca 2+ release, but had no effect on cytosolic STIM1 translocation evoked by thapsigargin. The inhibition of Mib on ORAI channels is structure-related, since other T-type Ca 2+ channel blockers with different structures, such as ethosuximide and ML218, had no or very small effect on ORAI channels. Moreover, Mib inhibited cell proliferation, induced apoptosis and arrested cell cycle progression. Our results suggest that Mib is a potent extracellular ORAI channel blocker, which provides a new pharmacological profile for the compound in regulating cell growth and death as an anti-cancer drug. action site is located on the extracellular cell surface. High concentrations of Mib not only reduce SOCE but also inhibit Ca 2+ release from ER. Mib significantly inhibits cell proliferation and promotes cell apoptosis by arresting the progression of cell cycle from G1/G0 to S phase, and to G2/M phase. These findings provide a new pharmacological profile for Mib, which is commonly used as T-type Ca 2+ channel blocker and has recently been repurposed as an anti-cancer drug.
The Relation between Subitizable Symbolic and Non-Symbolic Number Processing over the Kindergarten School-Year.

A long-standing debate in the field of numerical cognition concerns the degree to which symbolic and non-symbolic processing are related over the course of development. Of particular interest is the possibility that this link depends on the range of quantities in question. Behavioral and neuroimaging research with adults suggests that symbolic and non-symbolic quantities may be processed more similarly within, relative to outside of, the subitizing range. However, it remains unclear whether this unique link exists in young children at the outset of formal education. Further, no study has yet taken numerical size into account when investigating the longitudinal influence of these skills. To address these questions, we investigated the relation between symbolic and non-symbolic processing inside versus outside the subitizing range, both cross-sectionally and longitudinally, in 540 kindergarteners. Cross-sectionally, we found a consistently stronger relation between symbolic and non-symbolic number processing within versus outside the subitizing range at both the beginning and end of kindergarten. We also show evidence for a bidirectional relation over the course of kindergarten between formats within the subitizing range, and a unidirectional relation (symbolic→non-symbolic) for quantities outside of the subitizing range. These findings extend current theories on symbolic and non-symbolic magnitude development by suggesting that non-symbolic processing may in fact play a role in the development of symbolic number abilities, but that this influence may be limited to quantities within the subitizing range. This article is protected by copyright. All rights reserved.
Effects of Levosimendan on Inflammation and Oxidative Stress Pathways in a Lipopolysaccharide-Stimulated Human Endothelial Cell Model

Levosimendan is a myocardial Ca2+ sensitizer and opener of ATP-dependent potassium channels with inotropic, vasodilating, and cardioprotective properties. It was originally developed for the treatment of acute decompensated heart failure, but its complex mechanism of action means that it could also play a role in organ protection in response to infection. Using an in vitro approach, we explored whether levosimendan administration influenced cell responses to lipopolysaccharide (LPS). Primary human umbilical vein endothelial cells were stimulated with 1 µg/ml LPS from Escherichia coli (E. coli). Cells were treated with levosimendan at 0, 0.1, 1, or 10 µM 3 hr later. Samples were taken 24 hr after treatment to measure cell necrosis, apoptosis, pro-inflammatory mediators (interleukin 6 [IL-6] and toll-like receptor 4 [TLR4]), and oxidative stress (total reactive oxygen species/reactive nitrogen species [ROS/RNS]). Levosimendan at 1 and 10 µM protected against LPS-induced endothelial cell death and reduced TLR4 expression (p < .05). All doses reduced levels of IL-6 and ROS/RNS (p < .05). Findings suggest that levosimendan may exert protective effects against endothelial cell death in this model via attenuation of inflammation and oxidative stress pathways. Future studies might explore the potential beneficial role of levosimendan in modulating molecular mechanisms triggered by infections.
Autumn bird migration phenology: A potpourri of wind, precipitation and temperature effects

Climate change has caused a clear and univocal trend towards advancement in spring phenology. Changes in autumn phenology are much more diverse, with advancement, delays, and ‘no change' all occurring frequently. For migratory birds, patterns in autumn migration phenology trends have been identified based on ecological and life‐history traits. Explaining interspecific variation has nevertheless been challenging, and the underlying mechanisms have remained elusive. Radar studies on non‐species‐specific autumn migration intensity have repeatedly suggested that there are strong links with weather. In long‐term species‐specific studies, the variance in autumn migration phenology explained by weather has, nevertheless, been rather low, or a relationship was even lacking entirely. We performed a spatially explicit time window analysis of weather effects on mean autumn passage of four trans‐Saharan and six intra‐European passerines to gain insights into this apparent contradiction. We analysed data from standardized daily captures at the Heligoland island constant‐effort site (Germany), in combination with gridded daily temperature, precipitation and wind data over a 55‐year period (1960–2014), across northern Europe. Weather variables at the breeding and stopover grounds explained up to 80% of the species‐specific interannual variability in autumn passage. Overall, wind conditions were most important. For intra‐European migrants, wind was even twice as important as either temperature or precipitation, and the pattern also held in terms of relative contributions of each climate variable to the temporal trends in autumn phenology. For the trans‐Saharan migrants, however, the pattern of relative trend contributions was completely reversed. Temperature and precipitation had strong trend contributions, while wind conditions had only a minor impact because they did not show any strong temporal trends. As such, understanding species‐specific effects of climate on autumn phenology not only provides unique insights into each species' ecology but also how these effects shape the observed interspecific heterogeneity in autumn phenological trends.
Imaging correlates of the Blood Brain Barrier disruption in HIV associated neurocognitive disorder and therapeutic implications.

OBJECTIVE We explored the role of Blood brain barrier (BBB) disruption in the pathogenesis of HAND in the context of fully suppressive cART using Dynamic contrast enhanced perfusion (DCE-P) MRI. DCE-P is a new MRI technique that measures capillary permeability as an indicator for BBB integrity. We hypothesized that virally suppressed incident HAND would be associated with an impaired BBB as determined by DCE-P. DESIGN METHODS:: K-trans, a metric derivative of DCE-Perfusion, was obtained from different regions of the brain in a cohort of 20 patients with HAND who were virally suppressed in both CSF and blood compared with CSF and blood markers of neuroinflammation as well as with neurometabolites derived from MR spectroscopy. RESULTS The K-trans data showed significantly impaired BBB in HAND patients when compared to the controls in the regions of the basal ganglia and anterior frontal white matter (both p < 0.0001). CSF neopterin and CSF/serum albumin ratio correlated positively with K-trans but not with blood levels. CONCLUSION This study indicates that HAND in the context of viral suppression is associated with BBB disruption and the DCE MR derived K-trans metric is a very sensitive parameter to identify the BBB disruption. The finding of region specific BBB disruption rather than globally and the lack of correlation with blood markers of neuroinflammation suggest that HIV and not systemic inflammation is driving the BBB disturbance and that the BBB disruption is a consequence of HIV already in the brain as opposed to HIV first causing BBB disruption then brain disease. OBJECTIVE HIV associated neurocognitive disorders (HAND) in the context of suppressive combination antiretroviral therapy (cART) still occurs. We explored the role of Blood brain barrier (BBB) disruption in the pathogenesis of HAND in the context of fully suppressive cART using advanced Dynamic contrast enhanced perfusion (DCE-P). DCE-P is a new sensitive MRI technique that measures capillary permeability as an indicator for BBB integrity. We therefore hypothesized that virally suppressed incident HAND would still be associated with an impaired BBB as determined by DCE-P.
It is time for the world to take COPD seriously: a statement from the GOLD board of directors

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world and it is thought that one in 10 of the adult global population have the disease [1]. Despite this, COPD has not received the level of attention it requires by Ministries of Health and health services, particularly in low- and middle-income countries (LMIC), where most of the people with this disease live and where there is limited access to spirometry to confirm the diagnosis, little effective therapy and minimal public health policy on prevention. In 2012 the World Health Assembly endorsed the “25 by 25 goal”, focusing on reducing premature deaths from noncommunicable disease (NCDs) by 25% by the year 2025 [2], but while the third United Nations (UN) high-level meeting on NCDs in September 2018 acknowledged that “action to realize the commitments made for the prevention and control of noncommunicable diseases is inadequate” many felt the political declaration lacked ambition and was a missed opportunity to address the global NCD epidemic. As COPD is a highly prevalent NCD, is the third most common cause of premature death and is highly preventable we, the Board of Directors of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), are especially concerned that the disease has not been taken seriously enough by the UN/World Health Organization (WHO): not enough is being done to address the increasing prevalence, morbidity and mortality caused by COPD and there is no coordinated strategy to encourage countries to prioritise and resource its prevention and management. We must work together to prevent the development of COPD by reducing exposure to risk factors, to ensure the diagnosis is made as early as possible and to ensure all patients around the world receive effective therapy http://bit.ly/2WDUPMp
DNA reveals European roots of the ancient Philistines.

In the Hebrew bible, the Philistines were much maligned. They were the archenemies of the Israelites, who fought Samson9s armies and sent Goliath into battle against David. "Philistine" is still a slur for an uncivilized barbarian. Now an international team of geneticists and archaeologists has found a new way to understand the Philistines. By analyzing DNA from 12th century B.C.E burials in the Philistines9s renowned city of Ashkelon, Israel, researchers have found that they were interlopers in the ancient Middle East. Their closest known kin were from ancient Sardinia, Greece, or Spain, the team reports this week in Science Advances.
Inspiratory Constraints and Ventilatory Inefficiency Are Superior to Breathing Reserve in the Assessment of Exertional Dyspnea in COPD

Abstract Combining measurements of impaired lung mechanics (inspiratory constraints) with an index of increased respiratory stimuli to metabolic demand (poor ventilatory efficiency) might enhance the ability of cardiopulmonary exercise testing (CPET) in exposing a mechanistic role for ventilation on exertional dyspnea in COPD. In addition to the standard approach to suggest ventilatory limitation to exercise – a low breathing reserve (1−(peak ventilation (V̇E)/maximal voluntary ventilation × 100 < 20%) – we assessed the presence of critical inspiratory constraints (end-inspiratory lung volume (EILV)/total lung capacity (TLC) ≥ 0.9) and ventilatory inefficiency (V̇E/CO2 output (V̇CO2) nadir > 34) in 288 patients with mild to very severe COPD (FEV1 ranging from 18 to 121% predicted). We found that ∼50% of the patients with preserved breathing reserve developed critical inspiratory constraints. A low breathing reserve was weakly related to a lower peak O2 uptake (V̇O2) and/or a higher dyspnea burden; for instance, patients with low breathing reserve but without critical inspiratory constraints had similar dyspnea and peak V̇O2 than those with preserved breathing reserve (p > 0.05). In contrast, critical inspiratory constraints and ventilatory inefficiency were strongly associated with a negative outcome (likelihood ratio = 42.3 and 47.7, respectively; p < 0.001). A multiple logistic regression analysis revealed that only EILV/TLC ≥ 0.9 and V̇E/V̇CO2 nadir >34 predicted a severely reduced peak V̇O2 due to a high dyspnea burden (p < 0.001). Measurements of dynamic mechanical constraints and ventilatory inefficiency during incremental CPET are key to determine the impact of COPD on dyspnea and exercise tolerance across the spectrum of disease severity.
Patients with pulse-synchronous tinnitus should be suspected to have elevated cerebrospinal fluid pressure

Objective This study was performed to evaluate the prevalence and clinical importance of elevated cerebrospinal fluid (CSF) pressure among patients with pulse-synchronous tinnitus. Methods Nineteen patients underwent height and weight measurements, routine otologic examinations, ear computed tomography, brain magnetic resonance imaging, fundus examination, and tinnitus score assessment. We analyzed the data with Fisher’s exact test, the t-test, and Pearson’s correlation. Results The mean age of the 19 patients was 39.2 ± 8.1 years (range, 27–54 years), and the mean body mass index was 22.2 ± 1.6 kg/m2 (range, 19.9–24.6 kg/m2). The proportion of patients with elevated CSF pressure was 68%. No significant correlation between the severity of tinnitus and CSF pressure was found. Lumbar puncture and oral administration of diuretics resulted in significant improvement in tinnitus. Conclusions If detailed physical and imaging examinations fail to detect the definite cause of pulse-synchronous tinnitus, a routine lumbar puncture should be performed to measure the CSF pressure. Elevated CSF pressure should be suspected in patients with pulse-synchronous tinnitus.