Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of risk assessment tools for suspected cancer in general practice: a cohort study.

BACKGROUND Diagnostic delay is deemed to account for an estimated 5000 to 10 000 extra cancer deaths each year in the UK. Many cancer patients do not have symptoms meeting national referral criteria for rapid investigation. Risk assessment tools (RATs) have been developed to assist GPs in selecting patient for cancer investigation. AIM To assess the usability and acceptability of lung and colorectal RATs, as well as subsequent resource use and cancer diagnoses. DESIGN AND SETTING Cohort study with nested qualitative study with 614 GPs from 165 practices in seven English cancer networks were provided with RATs applicable to patients aged ≥40 years with bowel or respiratory symptoms. In-depth interviews were conducted with 34 individuals (11 project managers and 23 GPs). METHOD The study measured the number of RATs used, and subsequent cancer investigations and diagnoses, over a 6-month period and compared these with the previous 6 months. RESULTS A total of 2593 RATs (1160 lung, 1433 colorectal) were completed. Compared with the preceding 6 months, there were 292 more chest X-rays, 104 extra 2-week chest clinic appointments, and 47 additional diagnoses of lung cancer. For suspected colorectal cancer, there were 304 more 2-week referrals, 270 more colonoscopies, and 10 more cancers identified. RATs appeared to help GPs in their selection of patients for cancer investigation. Users reported that RATs helped to confirm a need for investigation as well as allowing reassurance when investigation was not needed. CONCLUSION Use of RATs in primary care was accompanied by increased diagnostic activity and additional cancer diagnoses.
Creating an Illusion of Movement between the Hands Using Mid-Air Touch

Apparent tactile motion has been shown to occur on many contiguous parts of the body, such as the fingers, forearms, and back. More recently, the illusion has also been elicited on non-contiguous parts of the body, such as between one hand and the other, either when the hands are interconnected or not interconnected by an object (e.g., when holding a tablet or not). Here, we explore the reproducibility of the intermanual tactile illusion of movement between two free hands by employing mid-air tactile stimulation. We investigate the optimal parameters to generate a continuous and smooth motion using two arrays of ultrasound speakers and two stimulation techniques (i.e., static versus dynamic focal point). In the first experiment, we investigate the occurrence of the illusion when using a static focal point, and we define a perceptive model. In the second experiment, we examine the illusion using a dynamic focal point, defining a second perceptive model. Finally, we discuss the differences between the two techniques.
Outcome of Bevacizumab Therapy in Patients with Recurrent Glioblastoma Treated with Angiotensin System Inhibitors

ABSTRACT Purpose: Antihypertensive therapy may improve bevacizumab efficacy in cancer patients. We examined efficacy and toxicity of angiotensin system inhibitors (ASI) and other antihypertensive drugs in bevacizumab treated recurrent glioblastoma patients. Methods: We retrospectively combined a national prescription registry with a clinical database with recurrent glioblastoma patients (n = 243). Results: Patients who initiated ASI after bevacizumab (n = 26) showed a tendency towards improved progression-free survival and overall survival (OS) with hazard rate (HR) reductions (HR = 0.70 and HR = 0.79, respectively). Calcium antagonists during bevacizumab therapy significantly improved OS (HR = 0.57). Conclusions: Overall the study supports a potential beneficial effect of antihypertensive treatment on prognosis of bevacizumab treated glioblastoma patients.
Functional Genomics Analysis of Big Data Identifies Novel Peroxisome Proliferator–Activated Receptor &ggr; Target Single Nucleotide Polymorphisms Showing Association With Cardiometabolic Outcomes

Background—Cardiovascular disease and type 2 diabetes mellitus represent overlapping diseases where a large portion of the variation attributable to genetics remains unexplained. An important player in their pathogenesis is peroxisome proliferator–activated receptor &ggr; (PPAR&ggr;) that is involved in lipid and glucose metabolism and maintenance of metabolic homeostasis. We used a functional genomics methodology to interrogate human chromatin immunoprecipitation-sequencing, genome-wide association studies, and expression quantitative trait locus data to inform selection of candidate functional single nucleotide polymorphisms (SNPs) falling in PPAR&ggr; motifs. Methods and Results—We derived 27 328 chromatin immunoprecipitation-sequencing peaks for PPAR&ggr; in human adipocytes through meta-analysis of 3 data sets. The PPAR&ggr; consensus motif showed greatest enrichment and mapped to 8637 peaks. We identified 146 SNPs in these motifs. This number was significantly less than would be expected by chance, and Inference of Natural Selection from Interspersed Genomically coHerent elemenTs analysis indicated that these motifs are under weak negative selection. A screen of these SNPs against genome-wide association studies for cardiometabolic traits revealed significant enrichment with 16 SNPs. A screen against the MuTHER expression quantitative trait locus data revealed 8 of these were significantly associated with altered gene expression in human adipose, more than would be expected by chance. Several SNPs fall close, or are linked by expression quantitative trait locus to lipid-metabolism loci including CYP26A1. Conclusions—We demonstrated the use of functional genomics to identify SNPs of potential function. Specifically, that SNPs within PPAR&ggr; motifs that bind PPAR&ggr; in adipocytes are significantly associated with cardiometabolic disease and with the regulation of transcription in adipose. This method may be used to uncover functional SNPs that do not reach significance thresholds in the agnostic approach of genome-wide association studies.
A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.

BACKGROUND ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. OBJECTIVE To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. METHODS This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. RESULTS There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. CONCLUSION Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.
EEG Based Emotion Recognition by Combining Functional Connectivity Network and Local Activations

Objective: Spectral power analysis plays a predominant role in electroencephalogram-based emotional recognition. It can reflect activity differences among multiple brain regions. In addition to activation difference, different emotions also involve different large-scale network during related information processing. In this paper, both information propagation patterns and activation difference in the brain were fused to improve the performance of emotional recognition. Methods: We constructed emotion-related brain networks with phase locking value and adopted a multiple feature fusion approach to combine the compensative activation and connection information for emotion recognition. Results: Recognition results on three public emotional databases demonstrated that the combined features are superior to either single feature based on power distribution or network character. Furthermore, the conducted feature fusion analysis revealed the common characters between activation and connection patterns involved in the positive, neutral, and negative emotions for information processing. Significance: The proposed feasible combination of both information propagation patterns and activation difference in the brain is meaningful for developing the effective human–computer interaction systems by adapting to human emotions in the real world applications.
High-conductance contacts to functionalized molecular platforms physisorbed on Au(1 1 1)

The conductances of molecules physisorbed to Au(1 1 1) via an extended system are probed with the tip of a low-temperature scanning tunneling microscope to maximize the control of the junction geometry. Inert hydrogen, methyl, and reactive propynyl subunits were attached to the platform and stand upright. Because of their different reactivities, either non-bonding (hydrogen and methyl) or bonding (propynyl) tip-molecule contacts are formed. The conductances exhibit little scatter between different experimental runs on different molecules, display distinct evolutions with the tip-subunit distance, and reach contact values of 0.003–0.05 G0. For equal tip-platform distances the contact conductance of the inert methyl is close to that of the reactive propynyl. Under further compression, the inert species, hydrogen and methyl, are found to be better conductors. This shows that the current flow is not directly correlated with the chemical interaction. Atomistic calculations for the methyl case reproduce the conductance evolution and reveal the role of the junction geometry, forces and orbital symmetries at the tip-molecule interface. The current flow is controlled by orbital symmetries at the electrode interfaces rather than by the energy alignment of the molecular orbitals and electrode states. Functionalized molecular platforms thus open new ways to control and engineer electron conduction through metal-molecule interfaces at the atomic level.
Measuring Trivialization of Mental Illness: Developing a Scale of Perceptions that Mental Illness Symptoms are Beneficial

ABSTRACT Much of the extant research on representations of mental illness in the media have focused on stigmatization. The negative effects of these stigmatizing portrayals on individuals with mental illness are serious. However, recent scholarship has identified another phenomenon in the mediated portrayal of mental illness whereby these conditions are trivialized. As opposed to stigmatizing portrayals that make people with mental illness seem violent and incompetent, media portrayals that trivialize mental illnesses often treat the symptoms of these conditions (e.g., organizational ability for people with obsessive compulsive disorder or high energy levels for people with attention-deficit/hyperactivity disorder) as benefits, thereby diminishing the seriousness of these conditions. The aim of the present study was to develop a reliable and valid scale for assessing how individuals perceive symptoms of mental illnesses as benefits (and, thereby, trivialize these illnesses). Results across three studies support the existence of a reliable and valid measure whereby symptoms demark individuals with a mental illness as receiving a benefit. By establishing this scale, researchers will be better suited to assess the potential intersections and interaction of processes related to mental illness trivialization and stigmatization, both through media portrayals and through everyday interactions.
Nuclear Magnetic Resonance Lipoprotein Subclasses and the APOE Genotype Influence Carotid Atherosclerosis in Patients with Systemic Lupus Erythematosus

Objective. Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. Since the conventional lipid profile (total plasma cholesterol, triglycerides, low and high density lipoprotein cholesterol) is not consistently altered in SLE, we hypothesized that investigation of lipoprotein subclasses would improve prediction of risk of atherosclerosis in these patients. Methods. As a quantitative index of atherosclerosis, we measured the carotid intima-media thickness (IMT) in 68 patients with SLE and related the atherosclerosis to a detailed lipoprotein profile generated using nuclear magnetic resonance (NMR). We measured the cholesterol transported by the pool of remnant lipoproteins (RLPc) and evaluated the modulatory effect of the APOE genotype on the lipoprotein subclass profile and atherosclerosis associated with SLE. Results. Circulating lipoprotein remnant particles [RLPc and intermediate density lipoprotein (IDL)] were positively correlated with IMT, and among them, the indicator that explained 20.2% of the variability in carotid atherosclerosis measured in these patients was IDL, as assessed by NMR. Carriers of the APOE2 allele were at increased risk due to a significant accumulation of IDL particles. Conclusion. Lipoprotein subclasses are more associated with subclinical atherosclerosis in patients with SLE than the lipid variables that are routinely measured. The IDL fraction, which is significantly modulated by the APOE genotype, is the most strongly, significantly, and positively correlated with IMT.
Exploring Perceptions of a Computerized Cognitive Behavior Therapy Program in a U.S. Rural Western State

Computerized mental health interventions have the potential to address existing mental health care disparities in rural communities. The aim of this study was to conduct an exploratory examination on the acceptability of an interactive computerized cognitive behavior therapy program to reduce depressive symptoms for adults in a rural Western state. Partnering with the land-grant university Extension system and a state nonprofit organization, we identified and interviewed 18 key informants and conducted 19 focus groups in 15 rural communities to ascertain attitudes and perspectives about the program. Key informants were provided access to the Thrive program prior to the interviews. Focus group participants were provided a brief demonstration of the program and asked to provide feedback. Content analyses of interview and focus group transcripts yielded four general themes of program acceptability: privacy, accessibility, user-friendliness, and cultural inappropriateness. Overall, participants indicated that the Thrive program would be useful for many in their communities. They also reported that the program could be improved by making videos that better represent rural community members’ lifestyles and experiences. The study team members acted on these findings to improve the Thrive program for rural Western populations.
Modified Finite Difference Schemes on Uniform Grids for Simulations of the Helmholtz Equation at Any Wave Number

We construct modified forward, backward, and central finite difference schemes, specifically for the Helmholtz equation, by using the Bloch wave property. All of these modified finite difference approximations provide exact solutions at the nodes of the uniform grid for the second derivative present in the Helmholtz equation and the first derivative in the radiation boundary conditions for wave propagation. The most important feature of the modified schemes is that they work for large as well as low wave numbers, without the common requirement of a very fine mesh size. The superiority of the modified finite difference schemes is illustrated with the help of numerical examples by making a comparison with standard finite difference schemes.
Canine neutrophils cooperate with macrophages in the early stages of Leishmania infantum in vitro infection

Leishmania infantum is the aetiological agent of human visceral leishmaniasis and canine leishmaniasis, both systemic and potentially fatal diseases. Polymorphonuclear neutrophils (PMN) are the first cells to phagocyte this parasite at the inoculation site, but macrophages (MØ) are the definitive host cells, ensuring parasite replication. The interaction between dog MØ, PMN and L infantum promastigotes was in vitro investigated. It was observed that promastigotes establish contact with blood monocyte‐derived MØ mainly by the tip of the flagellum. These cells, that efficiently bind and internalize parasites, underwent major morphological changes, produced nitric oxide (NO) and released histone H1 in order to inactivate the parasite. Transfer of intracellular parasites from PMN to MØ was confirmed by flow cytometry, using L infantum expressing a green fluorescent protein. The interaction of MØ with L infantum‐infected PMN lead to NO production and release of extracellular traps, which may contribute to parasite containment and inactivation. This study highlights for the first time the diversity of cellular and molecular events triggered by the interaction between canine PMN and MØ, which can promote a reduction of parasite burden in the early phase of L infantum infection.
Statistical concerns about implementing a peri‐operative neuromuscular blockade management strategy – a reply

Dr. Crucitti raised the important question aboutwhether our findings on implementing a new strategy for neuromuscular blockade management and improved postoperative pulmonary complications [1] might be diminished after accounting for potential bias arising frommissing data. We analysed the effects of our quality improvement initiative in an imputed dataset. We conducted multiple imputations by chained equations, which is a wellestablished strategy to address concerns related to missing data [2] (Table 3 [1]). Dr. Crucitti highlights the limitations of propensity score matching: patients who cannot be matched are not analysed, which can lead to a reduction in the generalisability of study results. For this reason, we did not use this method in the primary analysis, in which we applied a multivariable logistic regression model. In addition, we conducted sensitivity analyses to address remaining concerns related to the generalisability of our findings in disease-entity and procedure-related sub-groups of patients. The main challenge in our quality improvement study relates to our approach of making comparisons of results obtained before vs. after our intervention. The crude incidence of the postoperative respiratory complication rate observed before vs. after our intervention (improving the use of neostigmine) may or may not be caused by our intervention bundle, but could be the consequence of background improvements, alterations in patients’ characteristics and changes in practice over time. To reduce these effects, exploratory interrupted times series analyses, the strongest of quasi-experimental research designs [3], was performed, and provided stable results that accounted for changes of the outcome independent of the intervention studied. Data are assessed for autocorrelation and are adjusted using methods such as Prais regression. These quasi-experiments evaluate interventions without the use of randomisation and, like a randomised controlled trial, aim to demonstrate robust causality between an intervention and an outcome [4]. In our study, interrupted time-series analysis supported our hypothesis of a decreasing effect of our quality improvement initiative on unwarranted usage of neostigmine and its side-effects on postoperative respiratory function.
Prolonged Cold-Ischemia Induces Necroptotic Cell Death in Ischemia Reperfusion Injury and Contributes to Primary Graft Dysfunction After Lung Transplantation.

Primary graft dysfunction (PGD), a major cause of morbidity after lung transplantation, is linked to ischemia-reperfusion injury (IRI). Other factors such as preceding brain death (BD), hemorrhagic shock (HS), and pre-engraftment lung management are also important. We hypothesized that a multi-hit isogenic mouse model of lung transplantation is more closely linked to PGD than IRI alone. Left lung transplants were performed between inbred mice. A one-hit model of IRI was established by inducing cold ischemia (CI) to the donor lung at 0°C for 1h, 72h or 96h. Multi-hit models were established by inducing 24h of HS and/or 3h of BD before 24h of CI. The recipients were sacrificed up to 7 days after transplant. In the one-hit model of IRI, up to 72h CI time resulted in mild cellular infiltration after 24h reperfusion, but extension of CI time to 96h resulted in increased airway epithelial necroptotic pathway activation. In contrast, all multi-hit models demonstrated significant PGD, characterized by variable levels of diffuse alveolar damage, increased cellular infiltration, and activation of inflammatory and necroptotic pathways. The degree of epithelial injury was graded mild in "BD+IRI", moderate in "HS+IRI" and severe in "HS+BD+IRI" groups. Thus, activation of necroptosis is a central event in IRI following prolonged CI, however it is insufficient to cause PGD alone. Multi-hit models of donor lung injury after IRI demonstrated evidence of diffuse alveolar damage consistent with PGD. Thus, pre-existing donor lung status may be more important than CI time alone for inflammatory pathway activation in this model.
Violence en route: Eritrean women asylum-seekers experiences of sexual violence while migrating to Israel

Abstract Migrating irregularly, without access to support, may increase female asylum-seekers’ vulnerability to sexual violence. In this study, the authors applied a public health lens to explore the risk for sexual violence experienced by female asylum-seekers en route from Eritrea to Israel. The study team conducted 13 in-depth interviews and 8 focus groups with Eritreans in Israel between April and September of 2013. Participants in the study described their experiences occurring in three segments. The combination of irregular movement through dangerous, difficult and often isolated terrain, dependence on human smugglers, and vulnerability to traffickers led to the systematization and normalization of sexual violence en route. Such factors heighten vulnerability to sexual violence among these Eritrean women asylum-seekers, as well as others who find themselves in similar circumstances.