Miracle-dz/UniFAR-FTUs huggingface dataset:
The safety and tolerability of beta blockers in heart failure with reduced ejection fraction: is the current underutilization of this evidence-based therapy justified?

Introduction: Beta blockers are one of the cornerstones for treatment of Heart Failure with Reduced Ejection fraction (HFRef), yet their use is often limited by adverse effects, either perceived or real. We performed a review of available data using PubMed.gov utilizing beta blocker, heart failure, reduced ejection fraction and safety as key words. Areas covered: Several well designed, large scale randomized clinical trials including CIBS-II (bisoprolol), MERIT-HF (metoprolol succinate), and Copernicus (carvedilol) among others, have been conducted in patients with HFRef and demonstrated an improvement in cardiac mortality and morbidity. Despite the preponderance of data supporting the use of beta blockers for patients HFRef, these medications remain underutilized and/or are often prescribed at lower than recommended dosages. Some of the reluctance to embrace beta blockade may be attributed to concern on the part of both the patient and prescriber about the non-cardiac adverse effects of this class of drugs. We have reviewed several recent reviews and meta-analyses of trials of beta blocker in heart failure which have conclusively demonstrated their tolerability in the populations studied. Expert opinion: In the final section of this paper we provide our opinions regarding initiating and optimizing beta blocker therapy for patients with HFRef.
Teaching university students to cook, to improve their diet: a pilot study at Nottingham Trent University

Objective: To determine if it is feasible to teach students to cook cheap nutritious food that they would want to reproduce in their own student residences. Design and methodology: A cohort of interested students was trained using the established ‘Let's Get Cooking’ model (www.letsgetcooking.org.uk 2012) which has been used in schools across England to establish cooking clubs within communities. These students developed a programme of four weeks of two-hour cookery lessons aimed at the student lifestyle. A pilot was run in the summer term of 2011 with lessons given to willing participants for free. The participants, both those who carried out the teaching and those who were taught were all asked to evaluate the pilot. In the following autumn a further course was run using some of the same ‘teachers’ but this time the students paid £12 (GBP) for the course of lessons. Results: The feedback from those taught to cook in the sessions was very favourable with 91% of respondents rating the sessions as excellent or good on six aspects of the course. All the participants felt their skills had improved and they felt more confident about cooking. On the second part of the pilot where the students had paid, 89% rated the sessions as excellent or good on the same criteria and 100% had enjoyed the sessions; 84% thought their skills had improved and 75% felt more confident about cooking after the course. Fifty per cent indicated that they would continue to cook healthy food after the sessions had ended. Conclusions and implications: Evidence suggests that many students have not learned to cook and do not eat healthily; however, they are prepared to pay and attend cookery classes aimed at their needs. What is not known is, if by empowering students to cook cheap healthy food, whether or not they will continue to do this after the classes have ended?
The safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure

ABSTRACT Introduction: Mineralocorticoid receptor antagonists (MRAs) have been accorded a class 1 indication for patients with chronic heart failure and a reduced left ventricular ejection fraction (HFREF) in both European and American guidelines. Uptake, however, has been less than optimal largely due to concerns about their safety, in particular the risk of hyperkalemia and renal dysfunction. Areas covered: This review presents the current state of affairs regarding the safety of MRAs in heart failure with reduced ejection fraction. Expert opinion: Careful patient selection and adherence to guideline-recommended inclusion and exclusion criteria, dosing, and serial monitoring of serum potassium and renal function, along with patient education regarding the potassium content of common foods, should minimize these risks and allow increased use of MRAs. Additionally, this may also result in a further reduction in cardiovascular mortality and hospitalizations for heart failure. The development of new non-steroidal MRAs, and especially new potassium binding molecules that are well tolerated and effective, hold the promise for increased safety and, therefore, increased and more prolonged use of MRAs in patients with heart failure, especially those with chronic kidney disease, diabetes mellitus, and the elderly.
Applications for site-directed molecular imaging agents coupled with drug delivery potential

Molecular imaging allows non-invasive characterization and quantification of biological processes at cellular and molecular level. Such technologies make it possible to enhance our understanding of drug activity and pharmokinetic properties, and therefore aid decisions to select candidates that are most likely to benefit from targeted drug therapy. Targeted DDSs are nanometer-sized carrier materials designed for improving the biodistribution of systemically applied (chemo-)therapeutics by strictly localizing its pharmacological activity to the site or organ of action. The parallel development of molecular imaging and targeted drug delivery offers great challenges and opportunities for a single multifunctional platform technology, combining targeted motif, therapeutic agents and imaging agents for imaging guided drug delivery. This review article summarizes the synthesis and characterization of various biomaterials that carry targeting motifs, imaging tags and therapeutic agents as theragnostics.
Risk factors of abnormal carbohydrate metabolism after pregnancy complicated by gestational diabetes mellitus

Objective: In gestational diabetes mellitus (GDM) abnormal glucose metabolism normalizes soon after delivery. However, the history of GDM predisposes to carbohydrate intolerance in the future. The aim of the study was to explore risk factors and to evaluate risk of glucose intolerance and diabetes mellitus in women with a history of GDM. Methods: 155 patients entered this case-control study. Participants fulfilled the inclusion criteria: a history of GDM, perinatal care in the study center. Medical and family history and laboratory findings were analyzed. Oral glucose tolerance test (OGTT) was performed. Results: 18.1% of patients presented impaired fasting glucose during the study, 20% presented impaired glucose tolerance and 23.2% presented diabetes mellitus. Gestational age at diagnosis of GDM, the results of OGTT during pregnancy, serum HbA1c concentration at 2nd and 3rd trimester, serum fructosamine concentration, symptoms of diabetic fetopathy in the neonate, the need for insulin therapy after delivery, maternal age at diagnosis of GDM and maternal body mass index before pregnancy were the significant risk factors of impaired glucose tolerance or diabetes in the future. Conclusion: GDM increases the risk of diabetes mellitus. Several risk factors of impaired carbohydrate metabolism can be distinguished in patients with a history of GDM.
Nanoparticles for biomedical imaging

Background: Synthetic nanoparticles are emerging as versatile tools in biomedical applications, particularly in the area of biomedical imaging. Nanoparticles 1 – 100 nm in diameter have dimensions comparable to biological functional units. Diverse surface chemistries, unique magnetic properties, tunable absorption and emission properties, and recent advances in the synthesis and engineering of various nanoparticles suggest their potential as probes for early detection of diseases such as cancer. Surface functionalization has expanded further the potential of nanoparticles as probes for molecular imaging. Objective: To summarize emerging research of nanoparticles for biomedical imaging with increased selectivity and reduced nonspecific uptake with increased spatial resolution containing stabilizers conjugated with targeting ligands. Methods: This review summarizes recent technological advances in the synthesis of various nanoparticle probes, and surveys methods to improve the targeting of nanoparticles for their application in biomedical imaging. Conclusion: Structural design of nanomaterials for biomedical imaging continues to expand and diversify. Synthetic methods have aimed to control the size and surface characteristics of nanoparticles to control distribution, half-life and elimination. Although molecular imaging applications using nanoparticles are advancing into clinical applications, challenges such as storage stability and long-term toxicology should continue to be addressed.
Fluorotic cervical compressive myelopathy, 20 years after laminectomy: A rare event

Background: Spinal cord compression in flourosis is a common complication. These complications are mainly due to compression of the spinal cord by thickening and ossification of posterior longitudinal ligament and ligamentum flavum. Surgical decompression is the treatment of choice for fluorotic spinal cord compression. The recurrence of spinal cord compression after surgical decompression in flourosis is a rare event. Case Description: We are presenting a case of a 63-year-old man who belonged to Kanpur, an endemic fluorosis region in India, with symptoms of cervical cord compression cranial to the operative site, 20 years after laminectomy for cervical fluorotic myelopathy. Urinary and serum fluoride levels were elevated. The patient underwent a skeletal survey: computed tomography and magnetic resonance imaging of the cervical spine showed a postoperative defect of laminectomy, osteosclerosis, osteophyte formation, calcification of the intraosseus membrane in the forearm, thickening and ossification of the posterior longitudinal ligament at C1, thickening and ossification of the residual ligamentum flavum at C1/C2, and dural calcification at the C2 vertebral level and compressive myelopathy. The patient refused surgical decompression and was managed with tizanidine HCl (an antispasticity medicine), a sublingual single night dose, 8 mg for symptomatic relief. Conclusion: The recurrence of spinal cord compression in the fluorotic spine 20 years after laminectomy is a very unusual event and hence the patient should be kept under observation for a long duration. This case report contributes to the literature associated with the management of fluorotic spine.
Liposomal cancer therapy: exploiting tumor characteristics

Importance of the field: More than 10 million people worldwide are diagnosed with cancer each year, and the development of effective cancer treatments is consequently of great significance. Cancer therapy is unfortunately hampered by severe dose-limiting side effects that reduce the efficacy of cancer treatments. In the search for more effective cancer treatments, nanoparticle-based drug delivery systems, such as liposomes, that are capable of delivering their drug payload selectively to cancer cells are among the most promising approaches. Areas covered in this review: This review provides an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What the reader will gain: The review focuses on strategies that exploit characteristic features of solid tumors, such as abnormal vasculature, overexpression of receptors and enzymes, as well as acidic and thiolytic characteristics of the tumor microenvironment. Take home message: It is concluded that the design of new liposomal drug delivery systems that better exploit tumor characteristic features is likely to result in more efficacious cancer treatments.
SLIC 2: Improved decision support for subaxial cervical spine injury

Mobile clinical decision support systems (mCDSS) have been described to improve adherence to guidelines. [3,4] For neurosurgery, a few mCDSS are available. Surgical Neurology International offers the most downloaded neurosurgical mCDSS for free from its website, in collaboration with DigitalNeurosurgeon.com. NeuroMind is currently available for iPhone, iPad, and Android, and offers many useful scores and some anatomical images for explanation to patients and medical students. SLIC is an app that offers evidence-based decision support for (the surgical treatment of) subaxial cervical spine injury. This app is only available for iPhone and has been developed in collaboration with Alexander Vaccaro and Marcel Dvorak. [1,5] More information on the first version of this app and its rationale has been published before in this journal. [2]
Emerging trend in nano-engineered polyelectrolyte-based surrogate carriers for delivery of bioactives

Importance of the field: In recent decades a new colloidal drug delivery system based on layer-by-layer (LbL) technology has emerged, which offers promising means of delivering bioactive agents, specifically biological macromolecules including peptides and DNA. Nano-engineered capsules specifically fabricated from biocompatible and biodegradable polyelectrolytes (PEs) can provide a better option for encapsulation of cells thereby protecting cells from immunological molecules in the body, and their selective permeability can ensure the survival of encapsulated cells. Areas covered in this review: This review encompasses a strategic approach to fabricate nano-engineered microcapsules through meticulous selection of polyelectrolytes and core materials based on LbL technology. The content of the article provides evidence for its wide array of applications in medical therapeutics, as indicated by the quantity of research and patents in this area. Recent developments and approaches for tuning drug release, biocompatibility and cellular interaction are discussed thoroughly. What the reader will gain: This review aims to provide an overview on the development of LbL capsules with specific orientation towards drug and macromolecular delivery and its integration with other drug delivery systems, such as liposomes. Take home message: Selection of PEs for the fabrication of LbL microcapsules has a profound effect on stability, drug release, biocompatibility and encapsulation efficacy. The release can be easily modulated by varying different physicochemical as well as physiological conditions. Scale-up approaches for the fabrication of LbL microcapsules by means of automation must be considered to improve the possibility of application of LbL microcapsules on a large scale.
Oligonucleotide delivery in cancer therapy

Importance of the field: Cancer is frequently caused by altered protein expression. Oligonucleotides (ONs) are short synthetic nucleic acid fragments, able to selectively correct protein expression into cells by different mechanisms. However, biological barriers hamper the therapeutic use of ONs without suitable delivery strategies. Areas covered in this review: This review summarizes the most meaningful non-viral strategies for ON delivery, including the chemical modifications of the ON backbone and non-viral delivery systems. What the reader will gain: The reader will gain an update of the main strategies for ON delivery in cancer. Advantages and limits of each approach are underlined. Emphasis is given to the delivery strategies that contributed to bringing ONs into clinical trials. Take home message: In the long story of ONs for cancer therapy, the development of delivery strategies has led, in the last few years, to different opportunities to use the high therapeutic potential of these molecules in humans.
Automated mitosis detection using texture, SIFT features and HMAX biologically inspired approach

Context: According to Nottingham grading system, mitosis count in breast cancer histopathology is one of three components required for cancer grading and prognosis. Manual counting of mitosis is tedious and subject to considerable inter- and intra-reader variations. Aims: The aim is to investigate the various texture features and Hierarchical Model and X (HMAX) biologically inspired approach for mitosis detection using machine-learning techniques. Materials and Methods: We propose an approach that assists pathologists in automated mitosis detection and counting. The proposed method, which is based on the most favorable texture features combination, examines the separability between different channels of color space. Blue-ratio channel provides more discriminative information for mitosis detection in histopathological images. Co-occurrence features, run-length features, and Scale-invariant feature transform (SIFT) features were extracted and used in the classification of mitosis. Finally, a classification is performed to put the candidate patch either in the mitosis class or in the non-mitosis class. Three different classifiers have been evaluated: Decision tree, linear kernel Support Vector Machine (SVM), and non-linear kernel SVM. We also evaluate the performance of the proposed framework using the modified biologically inspired model of HMAX and compare the results with other feature extraction methods such as dense SIFT. Results: The proposed method has been tested on Mitosis detection in breast cancer histological images (MITOS) dataset provided for an International Conference on Pattern Recognition (ICPR) 2012 contest. The proposed framework achieved 76% recall, 75% precision and 76% F-measure. Conclusions: Different frameworks for classification have been evaluated for mitosis detection. In future work, instead of regions, we intend to compute features on the results of mitosis contour segmentation and use them to improve detection and classification rate.
Mitosis detection using generic features and an ensemble of cascade adaboosts

Context: Mitosis count is one of the factors that pathologists use to assess the risk of metastasis and survival of the patients, which are affected by the breast cancer. Aims: We investigate an application of a set of generic features and an ensemble of cascade adaboosts to the automated mitosis detection. Calculation of the features rely minimally on object-level descriptions and thus require minimal segmentation. Materials and Methods: The proposed work was developed and tested on International Conference on Pattern Recognition (ICPR) 2012 mitosis detection contest data. Statistical Analysis Used: We plotted receiver operating characteristics curves of true positive versus false positive rates; calculated recall, precision, F-measure, and region overlap ratio measures. Results: We tested our features with two different classifier configurations: 1) An ensemble of single adaboosts, 2) an ensemble of cascade adaboosts. On the ICPR 2012 mitosis detection contest evaluation, the cascade ensemble scored 54, 62.7, and 58, whereas the non-cascade version scored 68, 28.1, and 39.7 for the recall, precision, and F-measure measures, respectively. Mostly used features in the adaboost classifier rules were a shape-based feature, which counted granularity and a color-based feature, which relied on Red, Green, and Blue channel statistics. Conclusions: The features, which express the granular structure and color variations, are found useful for mitosis detection. The ensemble of adaboosts performs better than the individual adaboost classifiers. Moreover, the ensemble of cascaded adaboosts was better than the ensemble of single adaboosts for mitosis detection.
The role of interferons in early pregnancy

Abstract The interferons (IFNs) form part of the large family of glycoproteins known as cytokines. They are secreted by host cells as a line of defence against pathogens and certain tumours. IFNs affect cell proliferation and differentiation and also play a very important role in the functioning of the immune system. Miscarriage in both humans has been associated with higher levels of IFN, particularly IFN-γ. However, this cytokine is evidently vital in successful murine pregnancies since it is involved in maintaining the decidual layer in addition to remodelling of the vasculature in the uterus. The effects of IFN on human pregnancies are more difficult to study. Hence, there is still a lot more to be discovered in the hope of reaching a definite conclusion regarding the impact of IFN
Cardiovascular disease risk factors associated with low level of physical activity in postmenopausal Polish women

Abstract Objectives: To determine whether physical activity level could have an effect on cardiovascular disease (CVD) risk factors in Polish postmenopausal women. Methods: We studied the associations of physical activity (PA) level with obesity indices, unfavorable lipid profile parameters and the insulin resistance index HOMA in 343 postmenopausal Polish women selected from an urban population, aged 50–60. Results: In the tested sample, a low level of PA significantly increased odds ratios for CVD risk factors such as BMI ≥ 30 kg/m2, total body fat (TBF) > 75th percentile, gynoid fat deposit (GFD) > 75th percentile, total cholesterol (TC) ≥ 5 mM, low-density lipoprotein cholesterol (LDL-C) > 3 mM and HOMA ≥ 1.95. Conclusions: Obesity and some metabolic CVD risk factors in postmenopausal women are directly associated with low PA level. Postmenopausal urban women should be persuaded to be physically active, as even moderate activity level seems to be sufficient to reduce the CVD risk in this group of individuals.
Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of women with endometriosis: a pilot study

Abstract Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors – Galectin-3 and Stimulation Expressed Gene 2 – in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7 ± 52.34 versus 21.05 ± 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis. Chinese abstract 由于并未明确的发病机制,子宫内膜异位症成为一种令人困惑的疾病。 一些研究认为腹腔液是子宫内膜异位发生和发展的关键炎症环境。 本研究分析了两种炎症因子-- 半乳糖凝集素3及刺激表达基因2在15名患有子宫内膜异位症妇女和8名对照妇女腹腔液中的水平。 腹腔液通过避免了任何污染的腹腔镜手术收集并妥善处理和保存，随后使用酶免疫分析法分析了浓缩腹腔液中的Gal-3和ST2。 异位症组的Gal-3水平明显高于对照组(64.7 ± 52.34 比 21.05 ± 20.83 ng/ml,p=0.044)，而ST2水平在两组中并无明显差异。 Gal-3与ST2水平存在明显的正相关，Gal-3水平与内异症的发展阶段、症状的持续时间、Marinoff及VAS评分正相关，而ST2与VAS评分呈正相关。 我们的结果显示Gal-3和ST2或与内异症炎症发展过程有关。 为确定子宫内膜异位症的早期诊断标记物及开展新的治疗方式仍需要进一步的研究。