Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastr

Introduction Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. Methods The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. Ethics/dissemination The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. Trial registration number ISRCTN39653756.
Opioids Misuse and Abuse: The Making of a National Opioid Epidemic.

The United States opioid epidemic has emerged as the premier public health crisis, with considerable effects on the medical and legal systems in the last 2 decades. These effects are most easily measured by the increase in opioid-related deaths, estimated at > 30,000 years.1 During this time frame, we have seen a 200% increase in opioid overdose-related deaths and 400% increase in the rate of prescription pain-related overdose in women.2,3 The pain epidemic is the primary culprit behind the prescription opioid epidemic. Chronic pain affects > 100 million Americans every year, resulting in a massive burden on the health care system. With financial cost estimates up to $635 billion per year, the annual US expenditure on pain is higher than those for cancer, heart disease, and diabetes combined.4,5 In the field of obstetrics and gynecology, pain is a common complaint and presents in numerous clinical settings—childbirth/postpartum period, perioperatively, and in the ambulatory clinic. Sharp increases in opioid prescribing, patient use, and misuse can be traced back to the early 2000s when pain was highlighted as an undertreated symptom. Nationwide pain relief was identified as a patient right and subsequently, pain was added as the “fifth vital sign” as part of a combined initiative between the Joint Commission on Accreditation of Healthcare Organizations and the Veterans Health Administration.6,7 Pain assessment was prioritized across all aspects of pain-acute, chronic, and malignant. Opioid prescriptions skyrocketed as a primary treatment for pain complaints. Although pain measurement continues to be an important component of patient assessment,
Molecular Repolarisation of Tumour-Associated Macrophages

The tumour microenvironment (TME) is composed of extracellular matrix and non-mutated cells supporting tumour growth and development. Tumour-associated macrophages (TAMs) are among the most abundant immune cells in the TME and are responsible for the onset of a smouldering inflammation. TAMs play a pivotal role in oncogenic processes as tumour proliferation, angiogenesis and metastasis, and they provide a barrier against the cytotoxic effector function of T lymphocytes and natural killer (NK) cells. However, TAMs are highly plastic cells that can adopt either pro- or anti-inflammatory roles in response to environmental cues. Consequently, TAMs represent an attractive target to recalibrate immune responses in the TME. Initial TAM-targeted strategies, such as macrophage depletion or disruption of TAM recruitment, have shown beneficial effects in preclinical models and clinical trials. Alternatively, reprogramming TAMs towards a proinflammatory and tumouricidal phenotype has become an attractive strategy in immunotherapy. This work summarises the molecular wheelwork of macrophage biology and presents an overview of molecular strategies to repolarise TAMs in immunotherapy.
AFF3: a new player in maintaining XIST monoallelic expression

The existence of highly differentiated X and Y chromosomes in mammals raises the issue of X-linked gene dosage compensation between XX females and XY males to avoid what would be similar to a monosomy X in males (Veitia et al., 2015). Inactivation of one copy of the X chromosomes in females provides a dosage-compensation mechanism equalizing the expression of X-linked genes in males and females (Ohno et al., 1959; Lyon, 1961). However, a simple Xchromosome inactivation (XCI) would not ensure a balanced expression between Xlinked and autosomal genes (Figure 1). This can be achieved if genes on the active X undergo a two-fold upregulation (Ohno, 1967). Some evidence supports this idea (Veitia et al., 2015 and references therein). In placental mammals, the X chromosome to be inactivated is randomly chosen during embryonic development and is stably transmitted through cell generations. Early cytogenetic studies in mice harboring X chromosome rearrangements allowed the identification of a region containing a locus necessary and sufficient to trigger XCI when present in two copies. Accordingly, this region was called X inactivation center (Xic in mouse, XIC in human). In placental mammals, XCI relies on epigenetic factors and is initiated at XIC/Xic. An essential player of this process within the XIC locus is X-inactive specific transcript (XIST/Xist) gene, which encodes a long non-coding RNA that is transcribed in a female-specific monoallelic manner. It coats the inactive X, creating an ‘RNA cloud’ (Galupa and Heard, 2015). Although XCI is conserved between mouse and human, divergent strategies are employed to ensure monoallelic XIST/Xist expression. For instance, expression of Xist in the mouse is tightly regulated and involves random monoallelic upregulation in peri-implantation
Prognosis and Neuropathologic Correlation of Clinical Subtypes of Parkinson Disease

Importance Clinical subtyping of Parkinson disease at diagnosis is useful in estimating disease course and survival. Severity and rate of progression of neuropathologies are important determinants of clinical Parkinson subtypes. Objective To provide longitudinal clinical disease-course data and neuropathologic correlation for newly proposed Parkinson disease subtypes. Design, Setting, and Participants Retrospective cohort study of consecutive patients with autopsy-confirmed Parkinson disease who were regularly seen throughout their disease course by hospital specialists in the United Kingdom and donated their brain at death to the Queen Square Brain Bank between January 2009 and December 2017. Patients with additional neuropathologic diagnoses, monogenic forms of parkinsonism, or insufficiently detailed clinical information were excluded. Based on severity of motor symptoms, rapid eye movement sleep behavior disorder, and autonomic and cognitive function at diagnosis, patients were classified adapting a subtyping classification into mild-motor predominant, intermediate, or diffuse malignant subtypes. Main Outcomes and Measures Time from diagnosis to disease milestones (recurrent falls, wheelchair dependence, dementia, and care home placement) and death were compared between subtypes, and their risk was estimated using Cox hazard regression models. Severity and distribution of Lewy pathology and Alzheimer disease–related pathology were assessed using staging systems. Results From a total of 146 patients, 111 patients were included (67 men [60.4%]; mean [SD] age at diagnosis, 62.5 [11.5] years). The diffuse malignant subtype had earlier development of milestones and reduced survival. Cox proportional hazard regression showed an increased adjusted risk of any disease milestone (hazard ratio, 10.90; 95% CI, 5.51-21.58; P < .001) and death (hazard ratio, 3.65; 95% CI, 1.98-6.75; P < .001) in the diffuse malignant group. Age at diagnosis was the only additional variable with statistical significance (adjusted hazard ratio for death, 1.14; 95% CI, 1.11-1.17; P <.001). Staging of Lewy pathology and Alzheimer disease–related pathology did not differ between subtypes, although they showed different rates of progression, and the latter was associated with age at death. Conclusions and Relevance Parkinson clinical subtypes at diagnosis may estimate disease course and survival, which may be useful in providing a more accurate prognosis in individual patients in clinical practice and helping to stratify subgroups in clinical trials. Different severity and progression of neuropathologies are important determinants of Parkinson subtypes, and age at diagnosis should be included in future subtype classifications.
polyRAD: Genotype Calling with Uncertainty from Sequencing Data in Polyploids and Diploids

Low or uneven read depth is a common limitation of genotyping-by-sequencing (GBS) and restriction site-associated DNA sequencing (RAD-seq), resulting in high missing data rates, heterozygotes miscalled as homozygotes, and uncertainty of allele copy number in heterozygous polyploids. Bayesian genotype calling can mitigate these issues, but previously has only been implemented in software that requires a reference genome or uses priors that may be inappropriate for the population. Here we present several novel Bayesian algorithms that estimate genotype posterior probabilities, all of which are implemented in a new R package, polyRAD. Appropriate priors can be specified for mapping populations, populations in Hardy-Weinberg equilibrium, or structured populations, and in each case can be informed by genotypes at linked markers. The polyRAD software imports read depth from several existing pipelines, and outputs continuous or discrete numerical genotypes suitable for analyses such as genome-wide association and genomic prediction.
The role of simulation-based education in cardiology

### Learning objectives Simulation-based education (SBE) is a ‘technique and not a technology’ which aims to ‘replace or amplify real-life experiences with guided experience that evoke or replicate substantial aspects of the real world in a fully interactive environment’. 1 Many simulations within healthcare can achieve a high degree of fidelity in which participants behave and act in a manner in which they would in a real-life scenario.1 Despite the paucity of evidence underpinning the traditional apprenticeship model for training,1 most reviews discussing the potential of SBE in medical healthcare examine the evidence that SBE is either equivalent to or better than this traditional model. The purpose of the current review is to explore some of the wider educational principles underpinning the use of SBE in medical healthcare and to examine both the potential drivers and obstacles to the development of SBE in cardiology training, human factors training and in the maintenance of competency. Commonly used terminology in suimulation based education are summarised in table 1. In an ideal training programme, a novice learning a new practical skill would be guided by an expert through five different stages of skill acquisition described by Dreyfus and Dreyfus.2–6 In this model, the following four components will contribute to successful learning:
Chromium isotopes tracking the resurgence of hexavalent chromium contamination in a past-contaminated area in the Friuli Venezia Giulia Region, northern Italy

ABSTRACT The origin of a resurgent hexavalent chromium contamination in groundwater from a phreatic aquifer in the Friuli Venezia Giulia Region plain was investigated by chromium isotopic systematics. The area underwent a severe Cr(VI) contamination by industrial effluents in 1997, when Cr(VI) concentration in groundwater reached 4500 µg/L. In subsequent years the contamination naturally attenuated, totally disappearing in 2003. A renewal of water contamination was observed in 2008, Cr(VI) reaching 1560 µg/L. The δ53Cr value in groundwater and extracts from sediments was measured in 2009–2011, and it ranges between −3.21 and +0.21‰ and between −4.71 and +1.26‰, respectively. Due to the lack of geogenic Cr-sources, these data are interpreted as evidence of the subsequent oxidation through Mn-oxides of the Cr(III) hosted in the aquifer and originated by the reduction of the original industrial chromates. Cr(III) is characterized by negative δ53Cr, starting from the δ53Cr value around zero of Cr(VI) in industrial effluents. Oxidation liberates soluble Cr(VI) which is transported by groundwater and permeated soils. The complex Cr-isotopic vs. concentration distribution reflects both the new Cr(VI) reduction and dilution processes in the aquifer system. From an environmental point of view, the data raise concerns regarding the potential impact of past Cr(VI)-contamination.
Biofilms en cuevas turísticas: la Cueva de Nerja y la Cueva del Tesoro

11 paginas. -- 2 figuras. -- 41 referencias. -- Conferencia presentada en el Sexto Congreso Espanol sobre Cuevas Turisticas, celebrado en Nerja (Malaga), en septiembre/octubre de 2016. -- Descarga de las Actas en http://www.cuevasturisticas. es/cuevatur/docs/2016/pdf/LibroCuevastur2016.pdf
Dietary Factors Associated with Frailty in Old Adults: A Review of Nutritional Interventions to Prevent Frailty Development

Frailty syndrome is a medical condition that is characterised by a functional decline, usually from 65 years old on, and creates the need for assistance to perform daily living activities. As the population ages, the need for specialised geriatric care will increase immensely, and consequently, the need for specialised services for the care of these people will increase accordingly. From a nutritional point of view, to control or balance the nutritional status of residents will be essential in order to prevent sarcopenia and, consequently, frailty development. In this line, previous studies have highlighted the association among low energy intake, inadequate intake of protein and vitamin D, and an increased risk of frailty development. However, there is a lack of intervention studies on frail patients, especially in the realm of quality clinical trials. The few studies performed to date seem to indicate that there is a protective role of protein supplementation against frailty syndrome. In this regard, it is tempting to suggest daily 30 g protein supplements to prevent frailty. However, it is well established that excess protein can also be harmful; therefore, specific individual characteristics should be considered before prescribing these supplements. On the other hand, the relevance of other nutritional interventions, such as vitamin D, omega-3, and medium-chain triglycerides, is much more scarce in the literature. Therefore, we encourage the development of new clinical trials to carry out effective therapies to prevent frailty development.
Biomarkers and personalised medicine for asthma

Asthma is the most common chronic lung disease, affecting approximately 300 million people worldwide. Its prevalence has increased over the past 40 years [1]. Symptoms can be controlled by anti-inflammatory drugs and bronchodilators but, so far, the disease cannot be cured [1, 2]. Precision medicine and personalised therapy are major goals for chronic inflammatory diseases such as asthma. These two aims can only be achieved when the different subtypes of asthma can be precisely defined by robust diagnostic criteria. http://ow.ly/2rsy30mODVS
Population-Based Assessment of the Association Between Magnetic Resonance Imaging Background Parenchymal Enhancement and Future Primary Breast Cancer Risk.

PURPOSE To evaluate comparative associations of breast magnetic resonance imaging (MRI) background parenchymal enhancement (BPE) and mammographic breast density with subsequent breast cancer risk. PATIENTS AND METHODS We examined women undergoing breast MRI in the Breast Cancer Surveillance Consortium from 2005 to 2015 (with one exam in 2000) using qualitative BPE assessments of minimal, mild, moderate, or marked. Breast density was assessed on mammography performed within 5 years of MRI. Among women diagnosed with breast cancer, the first BPE assessment was included if it was more than 3 months before their first diagnosis. Breast cancer risk associated with BPE was estimated using Cox proportional hazards regression. RESULTS Among 4,247 women, 176 developed breast cancer (invasive, n = 129; ductal carcinoma in situ,n = 47) over a median follow-up time of 2.8 years. More women with cancer had mild, moderate, or marked BPE than women without cancer (80% v 66%, respectively). Compared with minimal BPE, increasing BPE levels were associated with significantly increased cancer risk (mild: hazard ratio [HR], 1.80; 95% CI, 1.12 to 2.87; moderate: HR, 2.42; 95% CI, 1.51 to 3.86; and marked: HR, 3.41; 95% CI, 2.05 to 5.66). Compared with women with minimal BPE and almost entirely fatty or scattered fibroglandular breast density, women with mild, moderate, or marked BPE demonstrated elevated cancer risk if they had almost entirely fatty or scattered fibroglandular breast density (HR, 2.30; 95% CI, 1.19 to 4.46) or heterogeneous or extremely dense breasts (HR, 2.61; 95% CI, 1.44 to 4.72), with no significant interaction (P = .82). Combined mild, moderate, and marked BPE demonstrated significantly increased risk of invasive cancer (HR, 2.73; 95% CI, 1.66 to 4.49) but not ductal carcinoma in situ (HR, 1.48; 95% CI, 0.72 to 3.05). CONCLUSION BPE is associated with future invasive breast cancer risk independent of breast density. BPE should be considered for risk prediction models for women undergoing breast MRI.
Formation of heterocyclic aromatic amines in doner kebab cooked with different methods at varying degrees of doneness

ABSTRACT This study was designed to determine the formation of heterocyclic aromatic amines (HCAs) in two different types of doner kebab (yaprak doner-YD or mix doner-MD) cooked with different cooking methods (gas or electric) at varying degrees of doneness (rare, medium, well-done). In doner samples, nine common HCAs (IQ, IQx, MeIQ, MeIQx, PhIP, 4,8-DiMeIQx, 7,8-DiMeIQx, AαC, MeAαC) were detected. Additionally, the changes in the HCA precursors were evaluated. The initial concentration of precursors gradually decreased with the increase in doneness degree due to degradation or possible contribution in the Maillard reaction to form HCA compounds as a result of heat treatment (p < 0.05). Creatine content decreased, while creatinine content increased because of the conversion reaction. The two most abundant HCA in doner samples were 4,8-DiMeIQx and IQ, which measured in the range of 0.020–2.865 ng g−1 and 0.052–0.513 ng g−1, respectively. Other detected HCAs were determined in especially well-done samples. In conclusion, the diversity and the amount of each HCA compound in doner kebab samples showed variation depending on the effect of doneness degree, doner kebab type or cooking methods (p < 0.05). Graphical Abstract
Stress and its causes in UK gastroenterologists: results of a national survey by the British Society of Gastroenterology

Aim Evaluation of stress and its causes in UK gastroenterologists, Design Questionnaire emailed to all 1932 medical members of the British Society of Gastroenterology. Results Of 567 respondents (29%), 107 (20%) graded their stress level as 4 or 5 out of 5. Stress levels correlated inversely with self-reported happiness levels (r=−0.60; p<0.001) and with hours slept per night (r=−0.23; p<0.01) and correlated directly with % time off-duty thinking about work (r=0.46; p<0001) and with proportion of nights with broken sleep (r=0.30; p<0.01). Due to stress over the past year, 21% of respondents reported one of the following: consulting their general practitioner (7%), attending occupational health (5%), taking planned time off (7%), taking anxiolytics/antidepressants (6%) and considering suicide (5.5%). These respondents had higher stress and lower happiness levels than the remainder. Stress levels were higher in women and in those working full time but had no other demographic associations. The main causes of stress were excessive clinical work (ranked highest by 47% and most commonly patient-related administration), working conditions beyond control (ranked highest by 15% and most commonly inadequate information technology systems, workspace and secretarial staff) and conflict (ranked highest by 9%). Of eight potential factors, happiness with work showed the closest associations with overall happiness (positive) and overall stress (negative) levels. Talking to someone at work about stress was ranked difficult or impossible by 35%. The highest ranked suggested solutions were relief from some duties and mentoring. Conclusions Stress is common and has objective correlates in UK gastroenterologists. The main cause is excessive workload.
The Use of Functional Near-Infrared Spectroscopy to Differentiate Alcohol-Related Neurodevelopmental Impairment

ABSTRACT Oxygenated (HBO) and deoxygenated hemoglobin (HBR) levels in the prefrontal cortex (PFC) were measured using functional near-infrared spectroscopy (fNIRS) to determine if PFC activity during a cognitive inhibition task distinguishes children with prenatal alcohol exposure (PAE, n = 26) from both typically developing controls (n = 19) and a contrast group of children with other neurobehavioral problems (n = 14). Despite showing evidence of increased PFC activity in the non-inhibitory condition relative to controls, children in the PAE group displayed reduced PFC HBO and increased HBR relative to both other groups in the inhibitory condition, suggesting reduced PFC activity but increased oxygen consumption without sufficient oxygen replacement.
Creating an Ideal Self: Representations of Infidels in the Late Medieval Anatolian Frontier Narratives

The grand epic narratives of the religious heroes of the Muslim conquest of Anatolia have been well-known repositories of the world views and ideologies of the frontier society of late medieval Asia Minor. This article investigates the representation of the “other” of various categories, such as Frenk, Rum, and Yunan, in epics such as the Battalnâme, the Danismendnâme, and the Saltuknâme, arguing that the representation of these groups primarily functions as a negative self-image, as an inversion of the ideals of the frontier communities, such as chivalry, justice, generosity, courage, and self-discipline. It draws special attention to the “companion figure” of the hero as a tool to promote gaza ideology while inviting conversion of non-Muslim