Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of D-dimer in predicting mortality in patients with community-acquired pneumonia.

AIM To determine whether D-dimer in patients with communityacquired pneumonia (CAP) can predict mortality risk better than standard biomarkers. METHODS White blood cell (WBC), C-reactive protein (CRP) and D-dimer in 129 patients with CAP were analyzed. The recommended Pneumonia Severity Index (PSI) score was used to classify CAP patients into five groups according to the severity of disease (Group PSI I-V), and for predicting mortality. Additionally, the patients were divided in surviving and non-surviving group. RESULTS White blood cell and CRP were not in correlation with the severity of CAP and the risk of mortality. The correlation between plasma D-dimer and severity of CAP was found (r=0.4993; p less than 0.001). The level of D-dimer was significantly higher in nonsurviving (2498.38 ± 1248.83 ng/mL) than in surviving patients (966.44 ± 968.73 ng/mL) (p less than 0.001). In predicting mortality risk, D-dimer showed sensitivity of 0.84 (cut of >1538 mg/mL), specificity 0.86 and AUC 0.859 (95%CI; 0.787-0.914). Pneumonia Severity Index in predicting of mortality risk for cut of > PSI III showed sensitivity of 0.92, specificity 0.62 and AUC 0.868 (95%CI; 0.797-0.921). There was no statistical difference between AUC of PSI and D-dimer (delta AUC= 0.00895) (p=0.9005). CONCLUSION Coagulation abnormalities were presented in older patients with severe infections and comorbidity. Plasma D-dimer correlated better than standard inflammatory markers with severity of disease and risk of mortality in patients with CAP. In predicting mortality risk, D-dimer did not show difference among the PSI score.
Safety and efficacy of a repositionable and fully retrievable aortic valve used in routine clinical practice: the RESPOND Study

Aims RESPOND is a prospective, open-label, single-arm study evaluating the outcomes following transcatheter aortic valve implantation (TAVI) with the repositionable and fully retrievable Lotus Valve used in routine clinical practice for the treatment of patients with aortic valve stenosis. Methods and results RESPOND enrolled 1014 patients at sites across Europe, New Zealand, and Latin America; 996 patients received a Lotus Valve (mean age: 80.8 years; 50.8% female; Society of Thoracic Surgeons score: 6.0 ± 6.9). Repositioning was attempted in 29.2% of patients, with 99% success. The rate of all-cause mortality in the intent-to-treat population at 30 days (primary endpoint) was 2.6% (P < 0.001 vs. pre-specified performance goal). Thirty-day clinical follow-up was completed for 97.3% of patients. Among patients who received a Lotus Valve, the 30-day overall and disabling stroke rates were 3.0% and 2.2%, respectively. The 30-day permanent pacemaker implantation rate was 30.0% in all patients, and 34.6% in pacemaker-naïve patients. Echocardiographic data at baseline and pre-discharge were assessed by an independent core laboratory. Mean aortic valve gradient declined from 37.7 ± 15.2 mmHg at baseline to 10.8 ± 4.6 mmHg at hospital discharge (P < 0.001). Aortic valve area increased from 0.7 ± 0.2 cm2 at baseline to 1.8 ± 0.4 cm2 at discharge (P < 0.001). At hospital discharge, paravalvular leak (PVL) was absent or trace in 92% of patients; no patients had severe PVL, 0.3% of patients exhibited moderate PVL, and 7.7% of patients had mild PVL. Clinical follow-up in RESPOND will extend to 5 years. Conclusion The results of RESPOND confirm the safety and efficacy of TAVI with the Lotus Valve in routine clinical practice. Trial registration ClinicalTrials.gov #NCT 02031302.
Expression of TGF-β1/mTOR signaling pathway in pathological scar fibroblasts

The aim of the present study was to detect the expression of the key molecules, including transforming growth factor-β1 (TGF-β1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) of TGF-β1/mammalian target of rapamycin (mTOR) pathway in pathological scar fibroblasts. Immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the expression of the key molecules TGF-β1, PI3K, Akt, mTOR in fibroblasts of normal skin tissue and pathological scar tissue. Immunofluorescence showed that the expression of TGF-β1, PI3K and Akt was significantly enhanced (P<0.05) in pathological scar fibroblasts, and mainly expressed in the cell nucleus, but not in normal skin tissue or fibroblasts. RT-PCR and western blot test results revealed that the TGF-β1, PI3K, Akt, and mTOR mRNA and protein expression in pathological scar fibroblasts were significantly higher (P<0.05) than in the normal skin tissue. Expression of the TGF-β1/mTOR signaling pathway in pathological scar fibroblasts was significantly increased. Data suggest that this expression may be an important mechanism for pathological scar formation.
Pulmonary persistence of graphene nanoplatelets may disturb physiological and immunological homeostasis

Accumulated evidence suggests that chronic pulmonary accumulation of harmful particles cause adverse pulmonary and systemic health effects. In our previous study, most of the graphene nanoplatelet (GNP) remained in the lung until 28 days after a single instillation. In this study, we sought to evaluate the local and systemic health effect after a long pulmonary persistence of GNP. As expected, GNP remained in the lung on day 90 after a single intratracheal instillation (1.25, 2.5 and 5 mg kg−1). In the lung exposed at the highest dose, the total number of cells and the percentage of lymphocytes significantly increased in the BAL fluid with an increase in both the number of GNP‐engulfed macrophages and the percentage of apoptotic cells. A Th1‐shifted immune response, the elevated chemokine secretion and the enhanced expression of cytoskeletal‐related genes were observed. Additionally, the expression of natriuretic‐related genes was noteworthy altered in the lungs. Moreover, the number of white blood cells (WBC) and the percentage of macrophages and neutrophils clearly increased in the blood of mice exposed to a 5‐mg kg−1 dose, whereas total protein, BUN and potassium levels significantly decreased. In conclusion, we suggest that the long persistence of GNP in the lung may cause adverse health effects by disturbing immunological‐ and physiological‐homeostasis of our body. Copyright © 2016 John Wiley & Sons, Ltd.
Medication Adherence

OBJECTIVE To define medication adherence and describe the limitations of various assessment methods, reasons for nonadherence to medications used to manage chronic illness, the impact of nonadherence to osteoporosis medications, and strategies for improving medication adherence. BACKGROUND Medication nonadherence is a major public health problem that adversely affects patient outcomes and increases health care utilization and costs. Postmenopausal osteoporosis is a chronic disease, and adherence to drug therapy used to manage the disease is as much of a challenge as it is in other chronic diseases. SUMMARY Medication adherence reflects both compliance and persistence. Direct assessment methods (e.g., observation, laboratory serum drug assays) are more accurate than indirect methods, but they are more costly and often impractical. Indirect methods include patient self-report and the use of prescription refill records, pill counts, and electronic monitoring devices. Medication adherence in patients with postmenopausal osteoporosis or other chronic illnesses is less than optimal. Adverse effects, financial constraints, mis-communication with the prescriber, and a perception that medications are unnecessary are among the possible reasons for medication nonadherence. Unintentional nonadherence is a passive process, often simply forgetting, and intentional nonadherence is an active process involving a deliberate choice, often based on adverse effects or a perceived lack of benefit. CONCLUSIONS Nonadherence to osteoporosis medications can adversely affect patient outcomes and increase health care utilization and costs. An individualized approach to improving medication adherence based on patient preferences and readiness to change is needed.
Are microRNAs Important Players in HIV-1 Infection? An Update

HIV-1 has already claimed over 35 million human lives globally. No curative treatments are currently available, and the only treatment option for over 36 million people currently living with HIV/AIDS are antiretroviral drugs that disrupt the function of virus-encoded proteins. However, such virus-targeted therapeutic strategies are constrained by the ability of the virus to develop drug-resistance. Despite major advances in HIV/AIDS research over the years, substantial knowledge gaps exist in many aspects of HIV-1 replication, especially its interaction with the host. Hence, understanding the mechanistic details of virus–host interactions may lead to novel therapeutic strategies for the prevention and/or management of HIV/AIDS. Notably, unprecedented progress in deciphering host gene silencing processes mediated by several classes of cellular small non-coding RNAs (sncRNA) presents a promising and timely opportunity for developing non-traditional antiviral therapeutic strategies. Cellular microRNAs (miRNA) belong to one such important class of sncRNAs that regulate protein synthesis. Evidence is mounting that cellular miRNAs play important roles in viral replication, either usurped by the virus to promote its replication or employed by the host to control viral infection by directly targeting the viral genome or by targeting cellular proteins required for productive virus replication. In this review, we summarize the findings to date on the role of miRNAs in HIV-1 biology.
Predictors and pattern of weaning and long-term outcome of patients with prolonged mechanical ventilation at an acute intensive care unit in North India

Objective This study aimed to examine the clinical characteristics, weaning pattern, and outcome of patients requiring prolonged mechanical ventilation in acute intensive care unit settings in a resource-limited country. Methods This was a prospective single-center observational study in India, where all adult patients requiring prolonged ventilation were followed for weaning duration and pattern and for survival at both intensive care unit discharge and at 12 months. The definition of prolonged mechanical ventilation used was that of the National Association for Medical Direction of Respiratory Care. Results During the one-year period, 49 patients with a mean age of 49.7 years had prolonged ventilation; 63% were male, and 84% had a medical illness. The median APACHE II and SOFA scores on admission were 17 and 9, respectively. The median number of ventilation days was 37. The most common reason for starting ventilation was respiratory failure secondary to sepsis (67%). Weaning was initiated in 39 (79.5%) patients, with success in 34 (87%). The median weaning duration was 14 (9.5 - 19) days, and the median length of intensive care unit stay was 39 (32 - 58.5) days. Duration of vasopressor support and need for hemodialysis were significant independent predictors of unsuccessful ventilator liberation. At the 12-month follow-up, 65% had survived. Conclusion In acute intensive care units, more than one-fourth of patients with invasive ventilation required prolonged ventilation. Successful weaning was achieved in two-thirds of patients, and most survived at the 12-month follow-up.
Cooperation and the Division of Labour

Cooperation is vital for maintaining the integrity of complex life forms. In many cases in nature cooperation manifests itself through constituent parts performing different, but complementary, functions. The vast majority of studies on the evolution of cooperation, however, look only at the special case in which cooperation manifests itself via the constituent parts performing identical tasks. In this paper we investigate a classof games inwhich thesocially optimalbehaviour hasthe property of being heterogeneous. We show that this class of games is equivalent to a region of ST space (the space of normalised two-player games characterised by the ‘sucker’ and ‘temptation’ payoffs) which has previously been dismissed. We analyse, through a simple group selection model, properties that evolving agents would need to have in order to “solve” this dilemma. Specifically we find that positive assortment on pure strategies may lower mean individual payoff, and that assortment on mixed strategies will increase payoff, but not maximise it.
Term context models for information retrieval

At their heart, most if not all information retrieval models utilize some form of term frequency.The notion is that the more often a query term occurs in a document, the more likely it is that document meets an information need. We examine an alternative. We propose a model which assesses the presence of a term in a document not by looking at the actual occurrence of that term, but by a set of non-independent supporting terms, i.e. context. This yields a weighting for terms in documents which is different from and complementary to tf-based methods, and is beneficial for retrieval.
Estrogen and androgen-converting enzymes 17β-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17β-hydroxysteroid dehydrogenase type 1, 2, and breast cancer

Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-α, responsible for promoting the growth of the tissue. Further, 60-80% express the androgen receptor, which has been shown to have tissue protective effects in estrogen receptor positive breast cancer, and a more ambiguous response in estrogen receptor negative breast cancers. In this review, we summarize the function and clinical relevance in cancer for 17β-hydroxysteroid dehydrogenases 1, which facilitates the reduction of estrone to estradiol, dehydroepiandrosterone to androstendiol and dihydrotestosterone to 3α- and 3β-diol as well as 17β-hydroxysteroid dehydrogenases 2 which mediates the oxidation of estradiol to estrone, testosterone to androstenedione and androstendiol to dehydroepiandrosterone. The expression of 17β-hydroxysteroid dehydrogenases 1 and 2 alone and in combination has been shown to predict patient outcome, and inhibition of 17β-hydroxysteroid dehydrogenases 1 has been proposed to be a prime candidate for inhibition in patients who develop aromatase inhibitor resistance or in combination with aromatase inhibitors as a first line treatment. Here we review the status of inhibitors against 17β-hydroxysteroid dehydrogenases 1. In addition, we review the involvement of 17β-hydroxysteroid dehydrogenases 4, 5, 7, and 14 in breast cancer.
Parallelized cytoindentation using convex micropatterned surfaces.

Here we present a high-throughput, parallelized cytoindentor for local compression of live cells. The cytoindentor uses convex lens-induced confinement (CLiC) to indent micrometer-sized areas in single cells and/or populations of cells with submicron precision. This is accomplished using micropatterned poly(dimethylsiloxane) (PDMS) films that are adhered to a convex lens to create arrays of extrusions referred to here as "posts. " These posts caused local deformation of subcellular regions without any evidence of cell lysis upon CLiC indentation. Our micropost arrays were also functionalized with glycoproteins, such as fibronectin, to both pull and compress cells under customized confinement geometries. Measurements of Chinese hamster ovary (CHO-K1) cell migration trajectories and oxidative stress showed that the CLiC device did not damage or significantly stress the cells. Our novel tool opens a new area of investigation for visualizing mechanobiology and mechanochemistry within living cells, and the high-throughput nature of the technique will streamline investigations as current tools for mechanically probing material properties and molecular dynamics within cells, such as traditional cytoindentors and atomic force microscopy (AFM), are typically restricted to single-cell manipulation.
An update on current and emerging therapies for epithelial ovarian cancer: Focus on poly(adenosine diphosphate-ribose) polymerase inhibition and antiangiogenesis

Epithelial ovarian cancer is the leading cause of death from gynecologic tumors in western countries. Newly diagnosed epithelial ovarian cancer patients usually have good initial response to combination of platinum-based and taxane-based chemotherapy. However, most patients eventually experience relapses, and responses to subsequent therapies are generally short-lived. Intraperitoneal chemotherapy has been shown to improve survival outcomes, but toxicities and logistics limit its acceptance. Dose-dense schedule of paclitaxel combined with carboplatin remains controversial, and more studies are needed to validate this approach. About 15% of epithelial ovarian cancer patients carry gene mutations in BRCA1 and/or BRCA2. The development of poly(adenosine diphosphate-ribose) polymerase inhibitors represents a novel therapeutic strategy, in which poly(adenosine diphosphate-ribose) inhibition leads to the formation of double-stranded DNA breaks that cannot be accurately repaired in BRCA1- or BRCA2-mutated tumors, thus leading to tumor cell death. This principle of synthetic lethality can be demonstrated by olaparib, an oral agent that inhibits the repair of single strand DNA breaks during DNA replication, causing defective homologous recombination and hence tumor cell death. Currently, many poly(adenosine diphosphate-ribose) inhibitors are in different phases of development. Furthermore, mechanisms of defective homologous recombination pathway may include other genetic and epigenetic abnormalities in addition to either germline or somatic BRCA1 and/or BRCA2 mutations, making these pathways as potential therapeutic targets. The clinical pharmacology, clinical efficacy, safety, administration issues of olaparib and current clinical development of poly(adenosine diphosphate-ribose) inhibitors are described in this article, along with an overview on the treatment options (including intraperitoneal chemotherapy and dose-dense chemotherapy) for epithelial ovarian cancer. On the other hand, overexpression of the vascular endothelial growth factor and increased angiogenesis are associated with the development and progression of epithelial ovarian cancer. Although there are some expected toxicities associated with antiangiogenesis, combination of bevacizumab and systemic chemotherapy improves the progression-free survival and response rate compared to chemotherapy alone. The clinical efficacy of adding bevacizumab and its safety for advanced epithelial ovarian cancer is also reviewed, with emerging data on antiangiogenesis therapy.
Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review

Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies or bioapplications now and in the future. In this review, we first describe recent endeavors to select aptamers towards live cancer cells via cell-SELEX. We then introduce several characteristic applications of selected aptamers, especially in imaging, drug delivery and therapy. In part, these advances have been made possible via synthesis of aptamer-based nanomaterials, which, by their sizes, shapes, and physicochemical properties, allow such aptamer-nanomaterial complexes to function as signal reporters or drug carriers. We also describe how these aptamer-based molecular tools contribute to cancer biomarker discovery through high-affinity recognition of membrane protein receptors.
Swift thermal reaction norm evolution in a key marine phytoplankton species

Temperature has a profound effect on the species composition and physiology of marine phytoplankton, a polyphyletic group of microbes responsible for half of global primary production. Here, we ask whether and how thermal reaction norms in a key calcifying species, the coccolithophore Emiliania huxleyi, change as a result of 2.5 years of experimental evolution to a temperature ≈2°C below its upper thermal limit. Replicate experimental populations derived from a single genotype isolated from Norwegian coastal waters were grown at two temperatures for 2.5 years before assessing thermal responses at 6 temperatures ranging from 15 to 26°C, with pCO2 (400/1100/2200 μatm) as a fully factorial additional factor. The two selection temperatures (15°/26.3°C) led to a marked divergence of thermal reaction norms. Optimal growth temperatures were 0.7°C higher in experimental populations selected at 26.3°C than those selected at 15.0°C. An additional negative effect of high pCO2 on maximal growth rate (8% decrease relative to lowest level) was observed. Finally, the maximum persistence temperature (Tmax) differed by 1–3°C between experimental treatments, as a result of an interaction between pCO2 and the temperature selection. Taken together, we demonstrate that several attributes of thermal reaction norms in phytoplankton may change faster than the predicted progression of ocean warming.
Molecular Genetic Manipulation of Sarcocystis neurona

Sarcocystis neurona is a member of the important phylum Apicomplexa and the primary cause of equine protozoal myeloencephalitis (EPM). Moreover, S. neurona is the best‐studied species in the genus Sarcocystis, one of the most successful parasite taxa, as virtually all vertebrate animals may be infected by at least one species. Consequently, scientific investigation of S. neurona will aid in the control of EPM and neurologic disease in sea mammals, while also improving our understanding of a prominent branch on the apicomplexan phylogenetic tree. These protocols describe methods that expand the capabilities to study this prominent member of the Apicomplexa. © 2018 by John Wiley & Sons, Inc.
The control of tonic pain by active relief learning

Tonic pain after injury characterises a behavioural state that prioritises recovery. Although generally suppressing cognition and attention, tonic pain needs to allow effective relief learning so that the cause of the pain can be reduced if possible. Here, we describe a central learning circuit that supports learning of relief and concurrently suppresses the level of ongoing pain. We used computational modelling of behavioural, physiological and neuroimaging data in two experiments in which subjects learned to terminate tonic pain in static and dynamic escape-learning paradigms. In both studies, we show that active relief-seeking involves a reinforcement learning process manifest by error signals observed in the dorsal putamen. Critically, this system also uses an uncertainty (‘associability’) signal detected in pregenual anterior cingulate cortex that both controls the relief learning rate, and endogenously and parametrically modulates the level of tonic pain. The results define a self-organising learning circuit that allows reduction of ongoing pain when learning about potential relief.