Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiplatelet therapy: new pharmacological agents and changing paradigms

Recurrent atherothrombotic events in patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI) are essentially platelet‐driven processes, underscoring the need for effective pharmacological platelet inhibition. Dual antiplatelet therapy with aspirin and clopidogrel has been, for over a decade, the mainstay of antiplatelet management in ACS/PCI. However, atherothrombotic events continue to occur in a relevant proportion of subjects despite the benefit of this combination, which has led to the clinical development of newer and more potent antiplatelet drugs. Two of these, prasugrel and ticagrelor, have been recently approved for clinical use. The scope of this manuscript is to provide an up‐to‐date overview on new antiplatelet drugs in the setting of ACS and PCI, including the most recent advances on newly approved agents as well as on emerging compounds in clinical development.
Supervision registers: Recent government policy and legislation

With the possible exception of the proposed supervised discharge, the supervision register is the most controversial current government initiative within the mental health field. This paper presents both the guidance issued by the NHS Executive and the concerns that the psychiatric profession has expressed. Time will tell whether the supervision register turns out to be a visionary policy that successfully allays public concerns over community care or an example of a bureaucratic response to an issue of inadequate resources.
Increased N‐terminal cleavage of alpha‐2‐antiplasmin in patients with liver cirrhosis

The activity of alpha‐2‐antiplasmin (α2AP), the main fibrinolytic inhibitor, is modified by N‐ and C‐terminal proteolytic cleavages. C‐terminal cleavage converts plasminogen‐binding α2AP (PB‐α2AP) into a non‐plasminogen‐binding derivative. N‐terminal cleavage by antiplasmin‐cleaving enzyme (APCE), a soluble, circulating derivative of fibroblast activation protein (FAP), turns native Met‐α2AP into Asn‐α2AP, which is more quickly crosslinked into fibrin.
Fast combustion waves and chemi-ionization processes in a flame initiated by a powerful local plasma source in a closed reactor

Results are presented from experimental studies of the initiation of combustion in a stoichiometric methane–oxygen mixture by a freely localized laser spark and by a high-current multispark discharge in a closed chamber. It is shown that, preceding the stage of ‘explosive’ inflammation of a gas mixture, there appear two luminous objects moving away from the initiator along an axis: a relatively fast and uniform wave of ‘incomplete combustion’ under laser spark ignition and a wave with a brightly glowing plasmoid behind under ignition from high-current slipping surface discharge. The gas mixtures in both the ‘preflame’ and developed-flame states are characterized by a high degree of ionization as the result of chemical ionization (plasma density ne≈1012 cm−3) and a high frequency of electron–neutral collisions (νen≈1012 s−1). The role of chemical ionization in constructing an adequate theory for the ignition of a gas mixture is discussed. The feasibility of the microwave heating of both the preflame and developed-flame plasma, supplementary to a chemical energy source, is also discussed.
Protecting the anaesthetised brain

Abstract The anaesthetized brain is vulnerable to ischaemic insults, which could result in neurological deficits ranging from neuropsychological disturbances to stroke and even death. The risk of perioperative brain injury is relatively high in cardiac, neurosurgical and major vascular surgery, although it has also rarely been reported in noncardiac nonneurosurgical operations. Besides underlying risk factors such as cerebrovascular disease, advanced age, and cardiovascular disease, anaesthesia and surgery per se could also be a contributory factor. The anaesthesiologist plays a pivotal role in protecting the anaesthetized brain, both by taking preventive measures and instituting brain protection strategies. Despite advances and breakthroughs in pharmacological neuroprotection in the laboratory, currently there is no drug, anaesthetic or non-anaesthetic, which is available for clinical use. The anaesthesiologist has to rely on non-pharmacological modalities and neuromonitoring to prevent intraoperative brain injury
Molecular evidence for maternal inheritance of the chloroplast genome in tea, Camellia sinensis (L.) O. Kuntze.

BACKGROUND Tea is the most consumed beverage worldwide after water. Yet very little is known about the genetics of tea in comparison with other crop species. Here we have taken advantage of the polymorphic nature of microsatellite DNA to investigate the mode of chloroplast inheritance in tea, Camellia sinensis (L.) O. Kuntze. This is important for the correct interpretation of phylogeny and introgression data as well as assessing the suitability of chloroplast transformation as a means for transgene containment in tea. RESULTS The study was based on six Japanese tea cultivars, namely Aj2, CK23, Hatsumomiji, Nka05, Yamanoibuki and Kanayamidori used to generate four informative families. The parental pairs in the crosses differed at a single chlroroplast locus with respect to an imperfect microsatellite repeat of 16 nucleotide bases. In agreement with earlier cytological studies, all 61 progeny displayed a cpDNA profile that was consistent with the maternal inheritance of chloroplasts in tea. CONCLUSIONS The data generated here provide the first molecular evidence of the plastid inheritance in tea. However, we suggest that additional families and polymorphic markers be screened for increasing the confidence in the observed maternal inheritance of chloroplasts in this important crop species.
On the variability of near-surface screen temperature anomalies in the 20 March 2015 solar eclipse

Near-surface air temperature (NSAT) anomalies during the 20 March 2015 solar eclipse are investigated at 266 UK sites, using operational data. The high density of observing sites, together with the wide range of ambient meteorological conditions, provided an unprecedented opportunity for analysis of the spatial variability of NSAT anomalies under relatively uniform eclipse conditions. Anomalies ranged from −0.03°C to −4.23°C (median −1.02°C). The maximum (negative) anomaly lagged the maximum obscuration by 15 min on average. Cloud cover impacted strongly on NSAT anomalies, with larger anomalies in clear-sky situations (p<0.0001). Weaker, but statistically significant, correlations were found with wind speed (larger anomalies in weaker winds), proximity to coast (larger anomalies at inland sites), topography (larger anomalies in topographical low points) and land cover (larger anomalies over vegetated surfaces). In this mid-morning eclipse, the topographical influences on NSAT anomalies were apparently dominated by variations in residual nocturnal inversion strength, as suggested by significant correlations between post-sunrise temperature and NSAT anomaly at clear-sky sites (larger negative anomalies with lower post-sunrise temperatures). The largest NSAT anomaly occurred at a coastal site where flow transitioned from onshore to offshore during the eclipse, in a situation with large coastal temperature gradients associated with antecedent nocturnal cooling. This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
Mass spectrometry as a quantitative tool in plant metabolomics

Metabolomics is a research field used to acquire comprehensive information on the composition of a metabolite pool to provide a functional screen of the cellular state. Studies of the plant metabolome include the analysis of a wide range of chemical species with very diverse physico-chemical properties, and therefore powerful analytical tools are required for the separation, characterization and quantification of this vast compound diversity present in plant matrices. In this review, challenges in the use of mass spectrometry (MS) as a quantitative tool in plant metabolomics experiments are discussed, and important criteria for the development and validation of MS-based analytical methods provided. This article is part of the themed issue ‘Quantitative mass spectrometry’.
Percutaneous spinal procedures

Percutaneous spinal procedures have diagnostic and/or therapeutic roles in the management of back pain.Discography remains the only test that can confirm if a component of the patients' pain arises from a particular disc.The value of therapeutic disc procedures remains controversial, as there are very few randomized controlled studies.Although lumbar facet joint injections for facet syndrome are an established procedure, the evidence for their efficacy is limited.Lumbar facet joint injections may be used to treat sciatic pain arising from synovial cysts arising from facet joints.
No evidence of correlation between p53 codon 72 polymorphism and risk of bladder cancer in Moroccan patients

Background: The p53 codon 72 polymorphism has been investigated extensively for its association with various cancers around the world. Several studies have investigated the association between p53 polymorphism at codon 72 and risk of developing bladder cancer, but the results are still controversial. Aim: The aim of our study was to evaluate the association between the p53 polymorphism and the bladder cancer risk among Moroccan patients. Materials and Methods: This study was carried out on fresh biopsies from 41 patients with bladder cancer confirmed and 38 blood samples from control donors. Deoxyribonucleic acid was genotyped by Allele-specific polymerase chain reaction using specific primers to each polymorphic variant. Results: Frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes among cases were 17%, 66%, and 17%, while in controls the frequencies of Arg/Arg, Arg/Pro and Pro/Pro were 15.8%, 63.2%, and 21%, respectively. The difference between cases and controls was not statistically significant. An increased risk of bladder cancer development was not clearly related to any polymorphic variant of the p53 Arg72Pro in our study group from Moroccan population. Moreover, the frequency of the Arg allele was higher (71.45%) than the Pro allele (28.55%) in high stage of bladder tumors, but this difference was statistically not significant. Conclusion: This study suggests that Arg allele could be more involved in developing bladder tumor in Moroccan population than the Pro allele. Therefore, enlarging the sampling will be necessary to confirm this association in Moroccan population.
Gas-phase reactivity of [Ca(formamide)]2+ complex: an example of different dynamical behaviours

In the present contribution, we have summarized our recent work on the comprehension of [Ca(formamide)]2+ complex gas-phase unimolecular dissociation. By using different theoretical approaches, we were able to revise the original (and typical for such kind of problems) understanding given in terms of stationary points on the potential energy surface, which did not provide a satisfactory explanation of the experimentally observed reactivity. In particular, we point out how non-statistical and non-intrinsic reaction coordinate mechanisms are of fundamental importance. This article is part of the themed issue ‘Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces’.
Intracanal management of a post traumatic perforative invasive cervical root resorption using calcium enriched matrix cement

Invasive cervical root resorption (ICR) is a consequence of a resorptive soft-tissue penetrating into dentin that starts below the gingival attachment and tends to be asymptomatic unless dental pulp involvement. Prompt diagnosis is the key to retention of the involved tooth. Treatment procedure includes non-surgical elimination of the resorptive soft-tissues and restoration of the cavity. In case of pulp involvement, endodontic treatment is indicated. This is a report of a non-surgical intra canal treatment case in a maxillary central incisor, which involved the pulp and was successfully treated with calcium enriched mixture (CEM) cement. Based on favorable long-term treatment outcomes, CEM cement may be a promising biomaterial in treatment of ICR cases.
Targeting of type I protein kinase A to lipid rafts is required for platelet inhibition by the 3′,5′‐cyclic adenosine monophosphate‐signaling pathway

Platelet adhesion to von Willebrand factor (VWF) is modulated by 3′,5′‐cyclic adenosine monophosphate (cAMP) signaling through protein kinase A (PKA)‐mediated phosphorylation of glycoprotein (GP)Ibβ. A‐kinase anchoring proteins (AKAPs) are proposed to control the localization and substrate specificity of individual PKA isoforms. However, the role of PKA isoforms in regulating the phosphorylation of GPIbβ and platelet response to VWF is unknown.
Sensor-augmented insulin pump therapy: results of the first randomized treat-to-target study.

BACKGROUND The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring (CGM), compared to using an insulin pump with standard blood glucose monitoring systems. METHODS This 6-month, randomized, multicenter, treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of >or=7.5%. Subjects were randomized to pump therapy with real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood glucose only (control group [CG]). Clinical effectiveness and safety were evaluated. RESULTS A1C levels decreased (P<0.001) from baseline (8.44+/-0.70%) in both groups (SG, -0.71+/-0.71%; CG, -0.56+/-0.072%); however, between-group differences did not achieve significance. SG subjects showed no change in mean hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase (P=0.001) in hypoglycemia AUC during the blinded periods of the study. The between-group difference in hypoglycemia AUC was significant (P<0.0002). Greater than 60% sensor utilization was associated with A1C reduction (P=0.0456). Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the CG group, P=0.04). CONCLUSIONS A1C reduction was no different between the two groups. Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use; however, there was no increase in hypoglycemia AUC or number of events in the SG group. Subjects with greater sensor utilization showed a greater improvement in A1C levels.
Alcohol use in adolescence: Identifying harms related to teenager's alcohol drinking

Objective: To examine experienced harms of alcohol drinking among Finnish teenagers using two methodologically different question sets: open‐ended versus structured questions. In this article, we further assess whether open‐ended questions lead to similar or different answers regarding alcohol‐related harms compared with structured questions. Method: Nationally representative data were obtained from two cross‐sectional surveys: Adolescent Health and Lifestyle Survey (AHLS) based on mailed questionnaires (2001) and the school‐based European School Project on Alcohol and Other Drugs (ESPAD) (2003). Samples comprised 14–16‐year‐olds in AHLS (n = 4766) and 15–16‐year‐olds in ESPAD (n = 3321). Results and conclusion: Teenagers report quite a variety of harms due to their own alcohol drinking. However, the most commonly reported alcohol‐related harms were substantially different, depending on the method of answering. Therefore, particular attention should be paid to the question method when researching alcohol‐related consequences among adolescents: open questions may prove useful in revealing many of the current harms of adolescent alcohol drinking, but these might fail to gain responses for issues considered sensitive, which in turn may be obtainable via closed questions. Adolescents' own experiences of alcohol‐related harms should be noted when planning and implementing interventions to prevent underage alcohol use and related harms.
The Role of Patent Medicine Sellers in Home Management of Childhood Malaria: A Situational Analysis of Experience in Rural Nigeria

Patent medicine sellers (PMS) play an important role in supplying the medication needs of the community particularly antimalaria. A situational analysis of the role of PMS in home management of malaria was carried out in four rural local government areas in Southwestern Nigeria using both cross sectional and observational study methods. The results showed that patent medicine stores constituted 76.2% of the medicine shops in the areas. The PMS provided not only drugs but also consultation services. Malaria constituted the commonest fever for which drugs were purchased. The most commonly mentioned drug best for malaria was the 4 aminoquinolone. Many (55.4%) of the PMS have received some form of training on malaria treatment. However, this was carried out in many instances (41.9%) by the shop owners to the apprentice PMS or shopkeepers. Health personnel were mentioned as trainers by only 27% of the PMS. The use of guidelines provided by PMS was infrequent and only 13.8% could produce the guideline at the time of survey. PMS would like to have more training on causes and recognition of malaria and antimalaria dosages. These topics were least taught. The rural PMS is important to the management of malaria. If quality training and supervision is provided to them, home management of malaria should improve.
Position paper: the science of deep specification

We introduce our efforts within the project ‘The science of deep specification’ to work out the key formal underpinnings of industrial-scale formal specifications of software and hardware components, anticipating a world where large verified systems are routinely built out of smaller verified components that are also used by many other projects. We identify an important class of specification that has already been used in a few experiments that connect strong component-correctness theorems across the work of different teams. To help popularize the unique advantages of that style, we dub it deep specification, and we say that it encompasses specifications that are rich, two-sided, formal and live (terms that we define in the article). Our core team is developing a proof-of-concept system (based on the Coq proof assistant) whose specification and verification work is divided across largely decoupled subteams at our four institutions, encompassing hardware microarchitecture, compilers, operating systems and applications, along with cross-cutting principles and tools for effective specification. We also aim to catalyse interest in the approach, not just by basic researchers but also by users in industry. This article is part of the themed issue ‘Verified trustworthy software systems’.
Evaluation of a glucose meter in determining the glycemic index of chinese traditional foods.

BACKGROUND The purpose of this study was to evaluate whether the Glucometer Elite((R)) meter (Bayer Diagnostics, Kyoto, Japan) (POG) could be used for determining the glycemic index (GI) values of Chinese traditional foods, compared with the YSI (Yellow Springs, OH) glucose analyzer (YSI). METHODS After consumption of either glucose or one of 11 test foods, the 2-h postprandial glucose responses were measured separately by POG and YSI. GI values and incremental area under the blood glucose response curve (IAUC) values were then calculated to make comparisons between POG and YSI. RESULTS The mean glucose concentration measured by POG was higher than that measured by YSI (5.54 +/- 0.03 vs. 5.30 +/- 0.03 mmol/L, P < 0.01). The mean IAUC calculated by POG data was also higher than that calculated by YSI data (112.93 +/- 4.04 vs. 106.76 +/- 4.06 mmol.min/L, P < 0.01). However, there were no differences in the mean GI value determined by POG and YSI data for each test food. CONCLUSIONS Although the glucose concentrations measured by POG were higher than that measured by YSI glucose analyzer, it seemed to be an appropriate instrument to determine the GI values of Chinese traditional foods. However, this conclusion should be cautiously applied to other kinds of glucose meters.
In vitro 3D model and miRNA drug delivery to target calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease in the Western population, claiming 17000 deaths per year in the United States and affecting 25% of people older than 65 years of age. Contrary to traditional belief, CAVD is not a passive, degenerative disease but rather a dynamic disease, where initial cellular changes in the valve leaflets progress into fibrotic lesions that induce valve thickening and calcification. Advanced thickening and calcification impair valve function and lead to aortic stenosis (AS). Without intervention, progressive ventricular hypertrophy ensues, which ultimately results in heart failure and death. Currently, aortic valve replacement (AVR), surgical or transcatheter, is the only effective therapy to treat CAVD. However, these costly interventions are often delayed until the late stages of the disease. Nonetheless, 275000 are performed per year worldwide, and this is expected to triple by 2050. Given the current landscape, next-generation therapies for CAVD are needed to improve patient outcome and quality of life. Here, we first provide a background on the aortic valve (AV) and the pathobiology of CAVD as well as highlight current directions and future outlook on the development of functional 3D models of CAVD in vitro We then consider an often-overlooked aspect contributing to CAVD: miRNA (mis)regulation. Therapeutics could potentially normalize miRNA levels in the early stages of the disease and may slow its progression or even reverse calcification. We close with a discussion of strategies that would enable the use of miRNA as a therapeutic for CAVD. This focuses on an overview of controlled delivery technologies for nucleic acid therapeutics to the valve or other target tissues.
Cerebrovascular complications of diabetes: focus on cognitive dysfunction.

The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes. Lastly, we propose a role for the innate immunity-mediated inflammation in neurovascular changes in diabetes.
Liquid crystalline tactoids: ordered structure, defective coalescence and evolution in confined geometries

Tactoids are liquid crystalline microdroplets that spontaneously nucleate from isotropic dispersions, and transform into macroscopic anisotropic phases. These intermediate structures have been found in a range of molecular, polymeric and colloidal liquid crystals. Typically only studied by polarized optical microscopy, these ordered but easily deformable microdroplets are now emerging as interesting components for structural investigations and developing new materials. In this review, we highlight the structure, property and transformation of tactoids in different compositions, but especially cellulose nanocrystals. We have selected references that illustrate the diversity and most exciting developments in tactoid research, while capturing the historical development of this field. This article is part of a discussion meeting issue ‘New horizons for cellulose nanotechnology’.