Miracle-dz/UniFAR-FTUs huggingface dataset:
Peptidylarginine Deiminase Type 4 and Methyl-CpG Binding Domain 4 Polymorphisms in Chinese Patients with Rheumatoid Arthritis

Objective. Peptidylarginine deiminase type 4 (PADI4) and methyl-CpG binding domain 4 (MBD4) are closely related with rheumatoid arthritis (RA). We hypothesized that PADI4 and MBD4 polymorphisms may contribute to RA susceptibility. Methods. We studied PADI4 rs2240340 G/A, PADI4 rs874881 C/G, MBD4 rs140693 G/A, and MBD4 rs2005618 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results. When the PADI4 rs2240340 GG homozygote genotype was used as the reference group, the AA genotype was associated with a significantly increased risk of RA. In the recessive model, when PADI4 rs2240340 GG/GA genotypes were used as the reference group, the AA homozygote genotype was associated with a significant increased susceptibility to RA. PADI4 rs874881 C/G was in complete linkage disequilibrium with PADI4 rs2240340 G/A. MBD4 rs140693 G/A and MBD4 rs2005618 T/C polymorphisms were not associated with the risk of RA. In stratification analyses, a significantly increased risk for RA associated with the PADI4 rs2240340 AA genotype was evident among older patients and patients who were anticitrullinated protein antibody (ACPA)-positive compared with the PADI4 rs2240340 GG/GA genotype. Conclusion. These findings suggest that the functional single-nucleotide polymorphism PADI4 rs2240340 G/A variant allele is associated with RA development, especially among older patients and ACPA-positive patients. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation by a larger study from a more diverse ethnic population is needed to confirm these findings.
Oral ulceration – aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic

Oral ulceration is a common complaint of patients attending out‐patient clinics. The aim of this review is to provide the gastroenterologist with a differential diagnosis of oral ulceration, and a practical guide for the management of recurrent aphthous stomatitis, including topical and systemic therapy. The association of recurrent aphthous stomatitis with Behçet's disease and other systemic disorders, including coeliac disease, is discussed. Recent evidence concerning the immunopathogenesis of Behçet's disease is reviewed, including renewed interest in the role of Streptococcus sanguis and possible infectious triggering of an inappropriate immunoinflammatory response, resulting in tissue damage. The efficacy and limitations of conventional treatment for this mutisystem disorder are outlined together with the potential role of novel biological agents, such as anti‐tumour necrosis factor‐α therapy. Oral ulceration, as a manifestation of inflammatory bowel disease and a complication of drug therapy, is described. Guidance is given concerning indications for referral of patients with oral ulceration to an oral physician/surgeon for further investigations, including biopsy if appropriate.
Code Generation for Efficient Query Processing in Managed Runtimes

In this paper we examine opportunities arising from the convergence of two trends in data management: in-memory database systems (imdbs), which have received renewed attention following the availability of affordable, very large main memory systems; and language-integrated query, which transparently integrates database queries with programming languages (thus addressing the famous 'impedance mismatch' problem). Language-integrated query not only gives application developers a more convenient way to query external data sources like imdbs, but also to use the same querying language to query an application's in-memory collections. The latter offers further transparency to developers as the query language and all data is represented in the data model of the host programming language. However, compared to imdbs, this additional freedom comes at a higher cost for query evaluation. Our vision is to improve in-memory query processing of application objects by introducing database technologies to managed runtimes. We focus on querying and we leverage query compilation to improve query processing on application objects. We explore different query compilation strategies and study how they improve the performance of query processing over application data. We take C# as the host programming language as it supports language-integrated query through the linq framework. Our techniques deliver significant performance improvements over the default linq implementation. Our work makes important first steps towards a future where data processing applications will commonly run on machines that can store their entire datasets in-memory, and will be written in a single programming language employing language-integrated query and imdb-inspired runtimes to provide transparent and highly efficient querying.
Intergenerational Cycle of Obesity and Diabetes: How Can We Reduce the Burdens of These Conditions on the Health of Future Generations?

Prepregnancy overweight or obesity and excessive gestational weight gain have been associated with increased risk of maternal and neonatal complications. Moreover, offspring from obese women are more likely to develop obesity, diabetes mellitus, and cardiovascular diseases in their lifetime. Gestational diabetes mellitus (GDM) is one of the most common complications associated with obesity and appears to have a direct impact on the future metabolic health of the child. Fetal programming of metabolic function induced by obesity and GDM may have intergenerational effect and thus perpetuate the epidemic of cardiometabolic conditions. The present paper thus aims at discussing the impact of maternal obesity and GDM on the developmental programming of obesity and metabolic disorders in the offspring. The main interventions designed to reduce maternal obesity and GDM and their ability to break the vicious circle that perpetuates the transmission of obesity and metabolic conditions to the next generations are also addressed.
The Impact of Patent Wars on Firm Strategy: Evidence from the Global Smartphone Market

We examine how patent wars affect firm strategy during ecosystem competition. Using data from the global smartphone industry, we show that smartphone vendors, even if they are not directly involved in the patent war, gradually shift their business focuses to markets with weak intellectual property rights protection. This shift is attenuated for firms with capabilities to countersue others and pronounced for vendors whose home markets have weak intellectual property rights protection. We also find that the shift of vendor strategy affects market shares of platforms in different countries. In particular, we find that market shares of Google’s Android phones and Microsoft’s Windows phones grow faster in markets with weak intellectual property rights protection because of stronger vendor support. This study contributes to the emerging patent strategy literature and the business ecosystem literature by shedding new light on the strategic actions ecosystem participants use to mitigate risks from their investmen.
Ensemble of feature-based and deep learning-based classifiers for detection of abnormal heart sounds

The goal of the 2016 PhysioNet/CinC Challenge is the development of an algorithm to classify normal/abnormal heart sounds. A total of 124 time-frequency features were extracted from the phonocardiogram (PCG) and input to a variant of the AdaBoost classifier. A second classifier using convolutional neural network (CNN) was trained using PCGs cardiac cycles decomposed into four frequency bands. The final decision rule to classify normal/abnormal heart sounds was based on an ensemble of classifiers combining the outputs of AdaBoost and the CNN. The algorithm was trained on a training dataset (normal= 2575, abnormal= 665) and evaluated on a blind test dataset. Our classifier ensemble approach obtained the highest score of the competition with a sensitivity, specificity, and overall score of 0.9424, 0.7781, and 0.8602, respectively.
Gaze field properties of eye position neurones in areas MST and 7a of the macaque monkey

Abstract The activity of parietal cortex neurones primarily related to eye position (EP neurones) was studied in macaque monkeys with the aim of precisely defining the neurones' gaze fields (GF) and comparing them in two functionally different areas, MSTd and 7a. Discharge rates of single neurones in the inferior parietal lobule and in the underlying cortex of the superior temporal sulcus were recorded in two Java monkeys while the animals fixated a steady visual target positioned at several different points on a video screen. The GFs were then drawn as a regression surface fitting the mean discharge rates. Cells tonically influenced by the angle of gaze were found in both areas. The GFs most often took the form of a nearly planar surface best characterized as a ramp tilted towards a hemifield or quadrant of the visual field, shifted eccentrically with respect to the straight ahead (primary position), and with a midpoint centred between 0 deg and 20 deg of gaze eccentricity and saturation between 10 deg and 35 deg. In a minority of cases, the discharge rate was nearly maximal at the primary position and decreased to a minimum within 35 deg of eccentricity. In other instances, the GFs were peaked surfaces, limited to a restricted part of visual space. EP neurones, while showing similar gaze fields in areas MST and 7a, were found intermingled with functionally different types of cells. The results suggest that EP neurones similar to those already described in several areas of the monkey parietal cortex are present also in area MST. These cells, by signalling the degree of gaze eccentricity from the primary position, encode gaze position in an orbito-centered frame extending up to 30–35 deg from the straight-ahead. The role of EP neurones might be to supply contiguous elements with a gaze eccentricity signal required for visuo-motor processes such as the control of tracking movements.
Partial Strategyproofness : An Axiomatic Approach to Relaxing Strategyproofness for Assignment Mechanisms

We present partial strategyproofness, a new, relaxed notion of strategyproofness to study the incentive properties of non-strategyproof assignment mechanisms. Under partially strategyproof mechanisms, truthful reporting is a dominant strategy for agents who have sufficiently different valuations for different objects. A single numerical parameter, the degree of strategyproofness, controls the extent to which agents’ valuations must differ. We show that the partial strategyproofness concept is axiomatically motivated, the underlying domain restriction is maximal, it can alternatively be defined in terms of partial dominance, it is intermediate between strategyproofness and many relaxed incentive concepts, and it unifies two prior local sufficiency results. Partial strategyproofness enables the comparison of important non-strategyproof mechanisms such as Probabilistic Serial, two variants of the Boston mechanism, the HBS Draft mechanism, and new hybrid mechanisms.
Folate Supplementation During Pregnancy Improves Offspring Cardiovascular Dysfunction Induced by Protein Restriction

Dietary protein restriction in the rat compromises the maternal cardiovascular adaptations to pregnancy and leads to raised blood pressure and endothelial dysfunction in the offspring. In this study we have hypothesized that dietary folate supplementation of the low-protein diet will improve maternal vascular function and also restore offspring cardiovascular function. Pregnant Wistar rats were fed either a control (18% casein) or protein-restricted (9% casein) diet ±5 mg/kg folate supplement. Function of isolated maternal uterine artery and small mesenteric arteries from adult male offspring was assessed, systolic blood pressure recorded, and offspring thoracic aorta levels of endothelial nitric oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams, vasodilatation to vascular endothelial growth factor was attenuated in the protein-restricted group but restored with folate supplementation, as was isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein restriction during pregnancy led to raised systolic blood pressure (P<0.01), impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during pregnancy prevented this elevated systolic blood pressure associated with a protein restriction diet. With folate supplementation, endothelium-dependent vasodilatation and endothelial NO synthase mRNA levels were not significantly different from either the control or protein-restricted groups. Maternal folate supplementation of the control diet had no effect on blood pressure or vasodilatation. This study supports the hypothesis that folate status in pregnancy can influence fetal development and, thus, the risks of cardiovascular disease in the next generation. The concept of developmental origins of adult disease focuses predominately on fetal life but must also include a role for maternal cardiovascular function.
A case study of convective organization into precipitating lines in the Southwest Amazon during the WETAMC and TRMM‐LBA

[1] A case study of convective development in the Southwest Amazon region during the Wet Season Atmospheric Mesoscale Campaign (WETAMC) and Tropical Rainfall Measuring Mission (TRMM)/Large-Scale Biosphere-Atmosphere (LBA) Experiment in Amazonia is presented. The convective development during 7 February 1999 is shown to occur during a period of very weak large-scale forcing in the presence of topography and deforestation. The available data include dual Doppler radar analysis, radiosonde launches, and surface and boundary layer observations. The observational analysis is complemented with a series of model simulations using the RAMS with 2-km resolution over a 300 km × 300 km area forced by a morning radiosonde profile. A comparison of the observed and simulated thermodynamic transformation of the boundary layer and of the formation of convective lines, and of their kinematic and microphysical properties is presented. It is shown that only a few very deep and intense convective cells are necessary to explain the overall precipitating line formation and that discrete propagation and coupling with upper atmosphere circulations may explain the appearance of several lines. The numerical simulation indicates that topography may be the cause of initial convective development, although later on the convective line is parallel to the midlevel shear. There are indications that small-scale deforestation may have an effect on increasing rainfall in the wet season when the large-scale forcing is very weak.
Muscle-damaging exercise 48 h prior to a maximal incremental exercise treadmill test reduces time to exhaustion: is it time to reconsider our pretest procedures?

ABSTRACT Pretest guidelines typically stipulate that no exercise should be performed 48 h prior to a maximal incremental exercise test. However, no study has specifically investigated if this timescale alters key outcome variables associated with . Twenty apparently healthy males split into two equal groups performed during three visits (visits 1 – EXP1, 2 – EXP2 and 4 – EXP3). The experimental group only, performed muscle-damaging exercise during visit 3. From EXP2 to EXP3 average time to exhaustion (TTE) decreased by 45 s (9%) (p < 0.01), maximum blood lactate decreased by 1.2 mmol/L (11%) (p = 0.03), and perceived readiness decreased by 8 mm (18%) (p = 0.01). There were no changes in any variables in the control group (p ≥ 0.37). Performing 48 h following muscle-damaging exercise impairs specific, but not all, physiological outcome variables.
Increased water contamination and grow-out Pekin duck mortality when raised with water troughs compared to pin-metered water lines using a United States management system

Controversy has developed as to whether or not pin-metered water lines or water troughs are more appropriate for Pekin ducks. We hypothesized that water troughs would show improved duck body conditions and environmental quality compared to pin-metered water lines. To test this hypothesis, we housed ducks in 2 barns, one with water lines and one with water troughs. Water troughs were constructed to meet RSPCA guidelines for number and density of ducks and with recently described verandas. Ducks were divided into 4 pens per barn (n = 1,000 ducks/pen). The study was then repeated (n = 8 pens per water source) in a cross-over design so the barns each contained the opposite water source to the first experiment. We scored the ducks’ body condition using an established scoring rubric and analyzed using SAS Proc GLM-Mix as binomial data. Ducks housed with water troughs showed higher (thus worse condition; P < 0.001) scores for eyes, nostrils, feather quality, feather cleanliness, and foot pads. We also compared water condition, water quality, and duck mortality using a Student t test for both water sources each week. We found that the water troughs showed higher iron (P < 0.001), nitrites (P < 0.001), pH (P < 0.01), and bacterial growth (P < 0.001). The bacterial growth was shown to have higher (P < 0.001) E. coli, coliforms, and Staphylococcus in the water troughs. Water lines typically showed no bacterial growth in culture-based assays. Ducks housed with water troughs used greater (P = 0.001) volumes of water compared to ducks housed with water lines. Ducks with water troughs also showed a greater percent (P = 0.008) mortality at all ages compared to ducks with water lines. These data suggest that water troughs may not be beneficial for duck welfare and could adversely impact both environment and duck or human health.
Estradiol inhibits ongoing autoimmune neuroinflammation and NFκB-dependent CCL2 expression in reactive astrocytes

Astroglial reactivity associated with increased production of NFκB-dependent proinflammatory molecules is an important component of the pathophysiology of chronic neurological disorders such as multiple sclerosis (MS). The use of estrogens as potential anti-inflammatory and neuroprotective drugs is a matter of debate. Using mouse experimental allergic encephalomyelitis (EAE) as a model of chronic neuroinflammation, we report that implants reproducing pregnancy levels of 17β-estradiol (E2) alleviate ongoing disease and decrease astrocytic production of CCL2, a proinflammatory chemokine that drives the local recruitment of inflammatory myeloid cells. Immunohistochemistry and confocal imaging reveal that, in spinal cord white matter EAE lesions, reactive astrocytes express estrogen receptor (ER)α (and to a lesser extent ERβ) with a preferential nuclear localization, whereas other cells including infiltrated leukocytes express ERs only in their membranes or cytosol. In cultured rodent astrocytes, E2 or an ERα agonist, but not an ERβ agonist, inhibits TNFα-induced CCL2 expression at nanomolar concentrations, and the ER antagonist ICI 182,170 blocks this effect. We show that this anti-inflammatory action is not associated with inhibition of NFκB nuclear translocation but rather involves direct repression of NFκB-dependent transcription. Chromatin immunoprecipitation assays further indicate that estrogen suppresses TNFα-induced NFκB recruitment to the CCL2 enhancer. These data uncover reactive astrocytes as an important target for nuclear ERα inhibitory action on chemokine expression and suggest that targeting astrocytic nuclear NFκB activation with estrogen receptor α modulators may improve therapies of chronic neurodegenerative disorders involving astroglial neuroinflammation.
Perceptions and knowledge regarding antimicrobial stewardship among clinicians in Jeddah, Saudi Arabia

Objectives: To understand the perceptions, attitude, and prescribing practices of clinicians regarding antimicrobial resistance (AMR). Methods: A multidisciplinary cross-sectional study comprising 447 clinicians of university, public, and private hospitals of Jeddah, Saudi Arabia was carried out from August to October 2014 using a self-administered questionnaire. Results: Interestingly, 33% of the general physicians yielded to patient/parent’s demand for the choice of antimicrobials (AMs) as compared with only 13.2% of the residents, and 4.3% of the specialists. In addition, expensive AMs are more often prescribed by the general physician (70.4%) in comparison with 26.4% residents and 30.4% of the specialists. However, no significant differences were observed between the knowledge and perceptions regarding the current scope of AM agents, as well as their use and misuse. Furthermore, dependability of specialist and residents seems to be significantly higher than general physicians on pocketbooks and smartphone for AM education sources. Conclusion: This study revealed that despite a clear concept of AMR, general physicians lacks consistency in prescribing aptitude and use of effective educational resources, while all respondents lacks dedication to follow the guidelines of AM use. This highlights the requirement of AM stewardship with decisive objective of reduction in AMR.
Identification of a Novel Type of Silk Protein and Regulation of Its Expression*

The silk of lepidopteran insects has been studied extensively as proteins of two categories: the fibroins, which are produced in the posterior section of silk glands, and the sericins, which are secreted in the middle section. We now describe a third category that is named seroins to accentuate the fact that both the sericin- and the fibroin-producing cells participate in seroin secretion. Using a probe derived from the N-terminal sequences of a 23-kDa components of Galleria mellonella silk, we isolated silk gland-specific cDNA encoding 167 amino acids, of which 17 constitute the signal peptide. The following 14 residues match the N-terminal sequences of the 23- and 22.5-kDa silk proteines. The reaction of these proteins with concanavalin A and the presence of two glycosylation sites in the seroin peptide sequence indicate that seroin is secreted in two forms that both contain a mannose-rich sugar moiety. Seroin is distinguished from other silk proteins by high proline content (34 residues or 20.26% by weight), lack of cysteines, and the presence of two kinds of short amino acid repeats. Theseroin gene is expressed in both the posterior and middle silk gland sections. The expression fluctuates during development in correlation with the feeding regime and the changes in hormone titers:seroin mRNA is high in the silk glands of feeding larvae, declines at ecdysis, reaches a maximum during cocoon spinning, and thereafter rapidly drops to an undetectable level. In vivo and in vitro experiments showed that the drop is caused by ecdysteroid hormones and is prevented by juvenile hormones. N-terminal sequencing of several silk proteins of Bombyx mori revealed that the 8- and 13-kDa proteins share 5 or 6 out of 10 identified amino acids with the N terminus of Galleriaseroin and obviously represent seroin homologues. The result suggests that seroin-type proteins are a general component of lepidopteran silk.