Miracle-dz/UniFAR-FTUs huggingface dataset:
Pain networks from the inside: Spatiotemporal analysis of brain responses leading from nociception to conscious perception

Conscious perception of painful stimuli needs the contribution of an extensive cortico‐subcortical network, and is completed in less than one second. While initial activities in operculo‐insular and mid‐cingulate cortices have been extensively assessed, the activation timing of most areas supporting conscious pain has barely been studied. Here we used intracranial EEG to investigate the dynamics of 16 brain regions (insular, parietal, prefrontal, cingulate, hippocampal and limbic) during the first second following nociceptive‐specific laser pulses. Three waves of activation could be defined according to their temporal relation with conscious perception, ascertained by voluntary motor responses. Pre‐conscious activities were recorded in the posterior insula, operculum, mid‐cingulate and amygdala. Antero‐insular, prefrontal and posterior parietal activities started later and developed during time‐frames consistent with conscious voluntary reactions. Responses from hippocampus, perigenual and perisplenial cingulate developed latest and persisted well after conscious perception occurred. Nociceptive inputs reach simultaneously sensory and limbic networks, probably through parallel spino‐thalamic and spino‐parabrachial pathways, and the initial limbic activation precedes conscious perception of pain. Access of sensory information to consciousness develops concomitant to fronto‐parietal activity, while late‐occurring responses in the hippocampal region, perigenual and posterior cingulate cortices likely underlie processes linked to memory encoding, self‐awareness and pain modulation. Hum Brain Mapp 37:4301–4315, 2016. © 2016 Wiley Periodicals, Inc.
Harnessing Voltage Margins for Energy Efficiency in Multicore CPUs

In this paper, we present the first automated system-level analysis of multicore CPUs based on ARMv8 64-bit architecture (8-core, 28nm X-Gene 2 micro-server by AppliedMicro) when pushed to operate in scaled voltage conditions. We report detailed system-level effects including SDCs, corrected/uncorrected errors and application/system crashes. Our study reveals large voltage margins (that can be harnessed for energy savings) and also large $V_{min}$ variation among the 8 cores of the CPU chip, among 3 different chips (a nominal rated and two sigma chips), and among different benchmarks.Apart from the $V_{min}$ analysis we propose a new composite metric (severity) that aggregates the behavior of cores when undervolted and can support system operation and design protection decisions. Our undervolting characterization findings are the first reported analysis for an enterprise class 64-bit ARMv8 platform and we highlight key differences with previous studies on x86 platforms. We utilize the results of the system characterization along with performance counters information to measure the accuracy of prediction models for the behavior of benchmarks running in particular cores. Finally, we discuss how the detailed characterization and the prediction results can be effectively used to support design and system software decisions to harness voltage margins for energy efficiency while preserving operation correctness. Our findings show that, on average, 19.4% energy saving can be achieved without compromising the performance, while with 25% performance reduction, the energy saving raises to 38.8%. CCS CONCEPTS• Hardware → Power and energy → Power estimation and optimization; • Hardware → Robustness → Hardware reliability → Process, voltage and temperature variations
Integrin-specific signaling pathways controlling focal adhesion formation and cell migration

The fibronectin (FN)-binding integrins α4β1 and α5β1 confer different cell adhesive properties, particularly with respect to focal adhesion formation and migration. After analyses of α4+/α5+ A375-SM melanoma cell adhesion to fragments of FN that interact selectively with α4β1 and α5β1, we now report two differences in the signals transduced by each receptor that underpin their specific adhesive properties. First, α5β1 and α4β1 have a differential requirement for cell surface proteoglycan engagement for focal adhesion formation and migration; α5β1 requires a proteoglycan coreceptor (syndecan-4), and α4β1 does not. Second, adhesion via α5β1 caused an eightfold increase in protein kinase Cα (PKCα) activation, but only basal PKCα activity was observed after adhesion via α4β1. Pharmacological inhibition of PKCα and transient expression of dominant-negative PKCα, but not dominant-negative PKCδ or PKCζ constructs, suppressed focal adhesion formation and cell migration mediated by α5β1, but had no effect on α4β1. These findings demonstrate that different integrins can signal to induce focal adhesion formation and migration by different mechanisms, and they identify PKCα signaling as central to the functional differences between α4β1 and α5β1.
Theoretical investigation of the degradation mechanisms in host and guest molecules used in OLED active layers

A feature of OLEDs that has to date received little attention is the prediction of the stability of the molecules involved in the electrical and optical processes. Here, we present computational results intended to aid in the development of stable systems. We identify degradation pathways and define new strategies to guide the synthesis of stable materials for OLED applications for both phosphorescent emitters and organic host materials. The chemical reactivity of these molecules in the active layers of the devices is further complicated by the fact that, during operation, they can be either oxidized or reduced (as they localize a hole or an electron) in addition to forming both singlet and triplet excitons.
DEPARTMENT OF ECONOMICS, MANAGEMENT AND STATISTICS UNIVERSITY OF MILAN – BICOCCA

In the paper a general framework for large scale modeling of macroeconomic and financial time series is introduced. The proposed approach is characterized by simplicity of implementation, performing well independently of persistence and heteroskedasticity properties, accounting for common deterministic and stochastic factors. Monte Carlo results strongly support the proposed methodology, validating its use also for relatively small cross-sectional and temporal samples. By means of the proposed approach, new insights on US money market dynamics during the subprime and euro area financial crises are achieved. Moreover, three common factors, bearing the interpretation of level, slope and curvature factors, are extracted from the term structure of OIS spreads; we find the latter conveying additional information, relatively to commonly used credit risk measures like the TED or the BAA-AAA corporate spreads, which might be exploited, also within a composite indicator, for the construction of a risk barometer and real-time macroeconomic forecasting. JEL classification: C22, E43, G01
Global Correlates of Cardiovascular Risk: A Comparison of 158 Countries

The aim of this study was a large-scale ecological analysis of nutritional and other environmental factors potentially associated with the incidence of cardiovascular diseases (CVDs) in the global context. Indicators of CVDs from 158 countries were compared with the statistics of mean intake (supply) of 60 food items between 1993 and 2011, obesity rates, health expenditure and life expectancy. This comparison shows that the relationship between CVD indicators (raised blood pressure, CVD mortality, raised blood glucose) and independent variables in the global context is influenced by various factors, such as short life expectancy, religiously conditioned dietary customs, the imprecision of some statistics and undernutrition. However, regardless of the statistical method used, the results always show very similar trends and identify high carbohydrate consumption (mainly in the form of cereals and wheat, in particular) as the dietary factor most consistently associated with the risk of CVDs. These findings are in line with the changing view of the causes of CVDs. Because only the statistics of raised blood glucose include people using medications and reflect true prevalence that is independent of healthcare, more objective data on the prevalence of CVDs are needed to confirm these observed trends.
Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab

Background Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number of malignancies. All clinical trials have excluded patients with significant preexisting autoimmune disorders (ADs) and only one has included patients with immune-related adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1 in such patients. Patients and methods Patients with advanced melanoma and preexisting ADs and/or major immune-related adverse events (irAEs) with ipilimumab (requiring systemic immunosuppression) that were treated with anti-PD-1 between 1 July 2012 and 30 September 2015 were retrospectively identified. Results One hundred and nineteen patients from 13 academic tertiary referral centers were treated with anti-PD-1. In patients with preexisting AD (N = 52), the response rate was 33%. 20 (38%) patients had a flare of AD requiring immunosuppression, including 7/13 with rheumatoid arthritis, 3/3 with polymyalgia rheumatica, 2/2 with Sjogren's syndrome, 2/2 with immune thrombocytopaenic purpura and 3/8 with psoriasis. No patients with gastrointestinal (N = 6) or neurological disorders (N = 5) flared. Only 2 (4%) patients discontinued treatment due to flare, but 15 (29%) developed other irAEs and 4 (8%) discontinued treatment. In patients with prior ipilimumab irAEs requiring immunosuppression (N = 67) the response rate was 40%. Two (3%) patients had a recurrence of the same ipilimumab irAEs, but 23 (34%) developed new irAEs (14, 21% grade 3-4) and 8 (12%) discontinued treatment. There were no treatment-related deaths. Conclusions In melanoma patients with preexisting ADs or major irAEs with ipilimumab, anti-PD-1 induced relatively frequent immune toxicities, but these were often mild, easily managed and did not necessitate discontinuation of therapy, and a significant proportion of patients achieved clinical responses. The results support that anti-PD-1 can be administered safely and can achieve clinical benefit in patients with preexisting ADs or prior major irAEs with ipilimumab.
Effects of six common dietary nutrients on murine intestinal organoid growth

The intestinal epithelium of the gastrointestinal (GI) tract constantly renews itself to absorb nutrients and provide protection for the body from the outside world. Since the intestinal epithelium is constantly exposed to various chemicals and dietary components, it is critical to determine which constituents promote or inhibit intestinal epithelium health and growth rate. Intestinal organoids, three-dimensional miniature models of the intestines, represent an ex vivo tool to investigate intestinal physiology and growth patterns. In this study, we measured the growth rates of murine intestinal organoids exposed to various concentrations of different dietary constituents. Results indicate that caffeic acid inhibited organoid growth in a concentration-dependent manner, curcumin exhibited variable effectiveness, and vitamin C had no effect on organoid growth.
Pr2FeCrO6: A Type I Multiferroic.

We synthesized double perovskite Pr2FeCrO6 by solid-state method. Analysis of its X-ray powder diffraction shows that the compound crystallizes in a centrosymmetric structure with space group Pbnm. Our X-ray photoelectron spectroscopy (XPS) studies show that all the cations are present in +3 oxidation state. Magnetization studies of Pr2FeCrO6 show that the material is paramagnetic at room temperature and undergoes a magnetic transition below TCM = 250 K. We observe clear magnetic hysteresis loop, for example, below 150 K. A low remnant magnetization Mr, ∼0.05 μB/f. u. , is inferred from the observed magnetic hysteresis loop. 57Fe Mössbauer study at 25 K shows a high hyperfine magnetic field of ∼53 T at the Fe nucleus, which corresponds to a magnetic moment of ∼6-7 μB/Fe. These two results together suggest a ferrimagnetic (nearly compensated or canted) ordering of the Fe moments. Mössbauer studies close to the ferrimagnetic ordering temperature suggest interesting magnetic relaxation effects. A dielectric anomaly observed at TCE = 453 K signals a ferroelectric ↔ paraelectric phase transition. We observe at room temperature a clear and well-defined ferroelectric hysteresis loop, PS = 1.04 μC/cm2, establishing ferroelectricity in the material. From these results, we conclude that Pr2FeCrO6 is a type I multiferroic (TCE > TCM).
Understanding Alpha Decay

I study the importance of alpha decay for the measurement of realized and conditional expected returns in asset pricing studies. Alpha decay refers to the reduction in abnormal expected returns (relative to an asset pricing model) in response to an anomaly becoming widely known among market participants. As decreases in alpha are associated (ceteris paribus) with positive realized returns, the econometrician may misinterpret these repricing returns as evidence that the anomaly will persist in the future. Because alpha decay is generally a nonstationary phenomenon, asset pricing tests that impose stationarity may lead to biased inference. I illustrate the importance of alpha decay using the most commonly studied anomalies in the asset pricing literature and find that the measured alpha differs from the true alpha by about 1.4% per year. I provide a simple formula to correct for this bias and show how to incorporate alpha decay tests into the standard asset pricing toolkit. This paper was accepted by David Simchi-Levi, management science.
Cord Care Practices: A Perspective of Contemporary African Setting

Background Cord care is the series of steps applied in handling of the umbilical cord after delivery of the new born. Globally, an estimated 4 million deaths occur annually within the first 4 weeks of life and 1.5 million of these deaths are attributable to infections. In Nigeria, studies have reported umbilical cord infections accounting for between 10 and 19% of neonatal admissions and resultant estimated 30–49% neonatal deaths. Hence, this study was conducted to assess the knowledge and practice of cord care within a contemporary setting. Methodology This was a cross-sectional study conducted among 324 mothers of children less than 59 months using a multistage sampling technique and SSPS version 20 was used for data analysis. Crude and adjusted odds ratios as well as 95% confidence interval were used in this study with a P-value of ≤0.05 considered statistically significant. Results The mean age of the mothers in the study was 27.5 ± 6 years with majority of them having good overall knowledge and practice of cord care. Factors such residence in rural community (AOR = 0.26; 95% CI = 0.0915–0.7230) and heath facility delivery (AOR = 7.0; 95% CI = 4.7877–9.3948) were predictors of cord care practices. Conclusion This study has brought to light the level of cord care practices with health facility delivery, place of residence, and knowledge of cord care as its determinants.
Robot‐assisted vs freehand pedicle screw fixation in spine surgery – a systematic review and a meta‐analysis of comparative studies

Medical robotics has progressively become more compelling in modern orthopaedic surgery. Several studies comparing robot‐assisted (RA) and freehand (FH) conventional techniques for pedicle screw fixation have been published, but the results are unclear. Here, we assessed current evidence regarding the efficiency, safety and accuracy of RA compared with FH techniques.
Influence of prior cyclic hardening on high temperature deformation and crack growth in type 316L (N) stainless steel

For power generating equipment subjected to cyclic loading at high temperature, crack growth could arise from the combinations of fatigue and creep processes. There is potential for the material to undergo hardening (or more generally changes of material state) as a consequence of cyclic loading. Results of an experimental study to examine the influence of prior cyclic hardening on subsequent creep deformation are presented for type 316L(N) stainless steel at 600°C. Experiments were also carried out to explore creep crack growth at constant load, and crack growth for intermittent cyclic loading. For the as-received material there is substantial primary creep (hardening) at constant load, while for the cyclically hardened material at constant load the creep curves show recovery, and increasing creep rate with increasing time. Specimens subjected to prior cyclic hardening were also used for a series of creep and creep-fatigue crack growth tests. These tests demonstrated that there was accelerated crack grow.
Correlation between aromatase expression in the eutopic endometrium of symptomatic patients and the presence of endometriosis

Objective To investigate whether aromatase expression in the eutopic endometrium correlates with the presence and severity of endometriosis in patients with infertility and/or dysmenorrhea undergoing laparoscopy and hysteroscopy. Patients The study involved 106 patients of reproductive age with symptoms of dysmenorrhea and infertility. Sixteen endometriosis-free asymptomatic patients were used as a control group. Methods Concomitant laparoscopy and hysteroscopy was carried out in all cases. An endometrial biopsy was taken to determine aromatase p450 expression by immunohistochemistry. Endometriosis was staged according to the American Society of Reproductive Medicine classification. Results Endometriosis was diagnosed by laparoscopy in 92/106 symptomatic patients. In this group, aromatase expression was detected in the eutopic endometrium of 66/92 patients with endometriosis (72%) and in 13/14 (95%) patients in the symptomatic, endometriosis-free group (P = 0.09). Aromatase expression was not detected in any patients from the control group. In the endometriosis group, aromatase expression was detected in the eutopic endometrium of 28/45 patients (62%) with American Society of Reproductive Medicine classification stage 1 of the disease, in 11/14 patients (78%) with stage II, 14/20 patients (70%) with stage III, and in 12/13 patients (92%) with stage IV; however, the difference was only statistically significant between stages I and IV (P = 0.04). Conclusion Aromatase expression in the endometrium was associated with the presence of dysmenorrhea and infertility irrespective of the presence of endometriosis. When endometriosis was present, however, there was a tendency for aromatase expression to be positively correlated with dysmenorrhea severity.
Uptake of direct‐acting antiviral treatment for chronic hepatitis C in Australia

A government‐funded interferon‐free direct‐acting antiviral (DAA) treatment programme for chronic hepatitis C virus (HCV) infection has been available in Australia since March 2016. This study assessed the levels and patterns of DAA treatment uptake during March‐December 2016 in Australia and described the key features in the development of the programme. All prescriptions in Australia are submitted to the Pharmaceutical Benefits Scheme by dispensing pharmacies. Data on dispensed DAA prescriptions for a longitudinal cohort of individuals, representing a 10% random sample of the Pharmaceutical Benefits Scheme database, were used for estimating DAA treatment uptake and subgroup analyses. The estimated number of 32 400 individuals initiated DAA treatment in 2016, equating to 14% of people with chronic HCV infection in Australia. Most commonly prescribed DAA regimens included sofosbuvir/ledipasvir (56%, n = 18 020), sofosbuvir + daclatasvir (39%, n = 12 600) and sofosbuvir + other agents (4%, n = 1220). Among individuals initiated DAA treatment, 66% (n = 21 430) were men, 43% (n = 13 870) were ≤50 years old and 36% (n = 11 670) had cirrhosis. DAA prescriptions were 62% (n = 20 080) by specialists, 19% (n = 6000) by general practitioners (GP) and 20% (n = 6320) by other physicians. Proportion of individuals prescribed DAA by GPs increased from 8% to 31% and proportion of individuals ≤50 years old increased from 28% to 61% between March and December. In conclusion, rapid treatment scale‐up was observed in the first 10 months of unrestricted DAA programme in Australia. The proportion of prescriptions by GPs increased over time, important for broadened access. A trend towards younger age treatment suggested the broadening of DAA‐treated population, potentially including individuals at higher risk of HCV transmission.
The role of tumor microenvironment in therapeutic resistance

Cancer cells undergo unlimited progression and survival owing to activation of oncogenes. However, support of the tumor microenvironment is essential to the formation of clinically relevant tumors. Recent evidence indicates that the tumor microenvironment is a critical regulator of immune escape, progression, and distant metastasis of cancer. Moreover, the tumor microenvironment is known to be involved in acquired resistance of tumors to various therapies. Despite significant advances in chemotherapy and radiotherapy, occurrence of therapeutic resistance leads to reduced efficacy. This review highlights myeloid cells, cancer-associated fibroblasts, and mesenchymal stem cells consisting of the tumor microenvironment, as well as the relevant signaling pathways that eventually render cancer cells to be therapeutically resistant.
Genomic Characterisation of the Indigenous Irish Kerry Cattle Breed

Kerry cattle are an endangered landrace heritage breed of cultural importance to Ireland. In the present study we have used genome-wide SNP array data to evaluate genomic diversity within the Kerry population and between Kerry cattle and other European breeds. Patterns of genetic differentiation and gene flow among breeds using phylogenetic trees with ancestry graphs highlighted historical gene flow from the British Shorthorn breed into the ancestral population of modern Kerry cattle. Principal component analysis (PCA) and genetic clustering emphasised the genetic distinctiveness of Kerry cattle relative to comparator British and European cattle breeds. Modelling of genetic effective population size (Ne) revealed a demographic trend of diminishing Ne over time and that recent estimated Ne values for the Kerry breed may be less than the threshold for sustainable genetic conservation. In addition, analysis of genome-wide autozygosity (FROH) showed that genomic inbreeding has increased significantly during the 20 years between 1992 and 2012. Finally, signatures of selection revealed genomic regions subject to natural and artificial selection as Kerry cattle adapted to the climate, physical geography and agro-ecology of southwest Ireland.