Miracle-dz/UniFAR-FTUs huggingface dataset:
Breast Cancer Treatment: A Review

Importance Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer. Observations Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2): hormone receptor positive/ERBB2 negative (70% of patients), ERBB2 positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer–specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive and ERBB2 positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor–positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients with ERBB2-positive tumors receive ERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performed. Increasingly, some systemic therapy is delivered before surgery. Tailoring postoperative treatment based on preoperative treatment response is under investigation. Metastatic breast cancer is treated according to subtype, with goals of prolonging life and palliating symptoms. Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for the other 2 subtypes. Conclusions and Relevance Breast cancer consists of 3 major tumor subtypes categorized according to estrogen or progesterone receptor expression and ERBB2 gene amplification. The 3 subtypes have distinct risk profiles and treatment strategies. Optimal therapy for each patient depends on tumor subtype, anatomic cancer stage, and patient preferences.
Normative Influences on the Role of Prescription Medicine Misuse among College Students in the United States

ABSTRACT Prescription medicine misuse is a growing problem in college campuses across the US. The Center for Disease Control (CDC) recently declared that the problem has reached epidemic proportions and is leading to a significant loss of lives every day. Norms-based public health campaigns that have been used in the past to address substance abuse issues among college students have had mixed success rates. Using the theory of normative social behavior, this study argues that a lack of focus on relevant mediators and moderators could be responsible for the failure of previous norms-based campaigns. Specifically, we test and support the mediating influence of perceived outcome expectations and injunctive norms on the effect of descriptive norms on intentions to misuse prescription medicines. In addition, perceived self-efficacy and trait reactance moderated the role of descriptive norms on outcome variables. Theoretical and practical implications of the findings are discussed.
Immunopathogenesis and biomarkers of recurrent atrial fibrillation following ablation therapy in patients with preexisting atrial fibrillation

ABSTRACT Introduction: Recurrent atrial fibrillation (RAF) following ablation therapy occurs in about 50% of patients. The pathogenesis of RAF is unknown, but is believed to be driven by atrial remodeling in the setting of background inflammation. Structural, electrophysiological and mechanical remodeling has been associated with atrial fibrillation (AF). Inflammation and fibrotic remodeling are the major factors perpetuating AF, as mediators released from the atrial tissues and cardiomyocytes due to mechanical and surgical injury could initiate the inflammatory process. In this article, we have critically reviewed the key mediators that may serve as potential biomarkers to predict RAF. Areas covered: Damage associated molecular patterns, heat shock proteins, inflammatory cytokines, non-inflammatory markers, markers of inflammatory cell activity, and markers of collagen deposition and metabolism are evaluated as potential biomarkers with molecular treatment options in RAF. Expert commentary: Establishing biomarkers to predict RAF could be useful in reducing morbidity and mortality. Investigations into the role of DAMPs participating in a sterile immune response may provide greater insight into the pathogenesis of RAF. Markers evaluating immune cell activity, collagen deposition, and levels of heat shock proteins show the greatest promise as potential biomarkers to predict RAF and develop novel therapies.
The role of implicit perceptual-motor costs in the integration of information across graph and text.

Strategies used to gather visual information are typically viewed as depending solely on the value of information gained from each action. A different approach may be required when actions entail cognitive effort or deliberate control. Integration of information across a graph and text is a resource-intensive task in which decisions to switch between graph and text may take into account the resources required to plan or execute the switches. Participants viewed a graph and text depicting attributes of two fictitious products and were asked to select the preferred product. Graph and text were presented: (1) simultaneously, side by side; (2) sequentially, where the appearance of graph or text was triggered by a button press, or (3) sequentially, where the appearance of graph or text was triggered by a saccade, thus requiring cognitive effort, memory, or controlled processing to access regions out of immediate view. Switches between graph and text were rare during initial readings, consistent with prior observations of perceptual "switch costs. " Switches became more frequent during re-inspections (80% of time). Switches were twice as frequent in the simultaneous condition than in either sequential condition (button press or saccade-contingent), showing the importance of perceptual availability. These results show that strategies used to gather information while reading a graph and text are not based solely on information value, but also on implicit costs of switching, such as effort level, working memory load, or demand on controlled processing. Taking implicit costs into account is important for a complete understanding of strategies used to gather visual information.
Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity

Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed liver fluke granulin (Ov-GRN-1) in pre-malignant lesions by undertaking programmed CRISPR/Cas9 knockout of the Ov-GRN-1 gene from the liver fluke genome. Deep sequencing of amplicon libraries from genomic DNA of gene-edited parasites revealed Cas9-catalyzed mutations within Ov-GRN-1. Gene editing resulted in rapid depletion of Ov-GRN-1 transcripts and the encoded Ov-GRN-1 protein. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult flukes, but the infection resulted in reduced pathology as evidenced by attenuated biliary hyperplasia and fibrosis. Not only does this report pioneer programmed gene-editing in parasitic flatworms, but also the striking, clinically-relevant pathophysiological phenotype confirms the role for Ov-GRN-1 in virulence morbidity during opisthorchiasis.
Cell-Free DNA Release by Mouse Fetal Membranes

Introduction: Cell-free “fetal” DNA is released from the placenta. Because the fetal membranes also arise from the trophectoderm layer of the blastocyst, these studies sought to test the hypothesis that the membranes also release cell-free DNA (cfDNA). Methods: Fetal membranes were harvested from pregnant CD-1 mice and cultured in 12-well plates containing media alone or with staurosporine and thapsigargin (apoptosis stimulators), Q-VD-OPh (caspase inhibitor), Trolox (vitamin E analog), and lipopolysaccharide and tumor necrosis factor α (TNFα; inflammatory mediators). The cfDNA in the media was extracted, quantified, and normalized for tissue weight. Media was used for a lactate dehydrogenase (LDH) assay. Membrane homogenates were used to assess activated caspase levels and the expression of DNA fragmentation factor B (DFFB) and BAX proteins. 5-Methylcytosine was assessed using a 5-mC DNA enzyme-linked immunosorbent assay. The cfDNA was used to stimulate interleukin 6 (IL6) release by J774A.1 mouse macrophage cells. Results: Increased cfDNA release at 6 and 21 hours occurred in parallel with increasing LDH levels. The cfDNA concentrations were significantly suppressed by Q-VD-OPh and Trolox and increased by thapsigargin and TNFα. Increased caspase activity was suppressed by Q-VD-OPh and increased by TNFα, thapsigargin, and staurosporine. The expression of BAX and DFFB proteins significantly increased by 21 hours. 5-Methylcytosine levels were significantly lower in fetal membranes and placentas and below detectable in the cfDNA released by the explants. The cfDNA-stimulated IL6 release by macrophage cells was suppressed by chloroquine, a Toll-like receptor 9 (TLR9) inhibitor. Conclusions: These studies have confirmed cfDNA release by the mouse fetal membranes; cfDNA was markedly hypomethylated and a robust stimulator of TLR9.
Assessment of Regional Cerebral Blood Volume in Acute Human Stroke by Use of Single-Slice Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Background and Purpose The purpose of this study was to evaluate the clinical usefulness of dynamic susceptibility contrast-enhanced MRI (DSC-MRI) in acute cerebral ischemia. Methods During bolus injection of gadolinium-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted images was recorded from one slice. Concentration-time curves and images of regional cerebral blood volume (rCBV) were calculated from this data set. DSC-MRI, MR angiography, conventional spin-echo MRI (SE-MRI), and CT were performed in 11 patients within 6 hours after stroke onset and before thrombolytic or anticoagulant treatment was begun. A follow-up MRI examination was performed 24 to 48 hours after stroke onset. Results In 7 of 11 patients (group 1) with territorial infarcts of the middle (n=6) or posterior cerebral artery (n=1), DSC-MRI showed reduced rCBV in the affected territory before conventional SE-MRI displayed ischemic lesions. DSC-MRI was helpful to differentiate severely ischemic tissue from peri-infarct p.
Global Synchronization of Coupled Fractional-Order Recurrent Neural Networks

This paper presents new theoretical results on the global synchronization of coupled fractional-order recurrent neural networks. Under the assumptions that the coupled fractional-order recurrent neural networks are sequentially connected in form of a single spanning tree or multiple spanning trees, two sets of sufficient conditions are derived for ascertaining the global synchronization by using the properties of Mittag–Leffler function and stochastic matrices. Compared with existing works, the results herein are applicable for fractional-order systems, which could be viewed as an extension of integer-order ones. Two numerical examples are presented to illustrate the effectiveness and characteristics of the theoretical results.
Multigenerational prediction of genetic values using genome-enabled prediction

The identification of elite individuals is a critical component of most breeding programs. However, the achievement of this goal is limited by the high cost of phenotyping and experimental research. A significant benefit of genomic selection (GS) to plant breeding is the identification of elite individuals without the need for phenotyping. This study aimed to propose different calibration strategies using combinations between generations from different genetic backgrounds to improve the reliability of GS and to investigate the effects of LD in different types of mating systems: outcrossing (An) self-pollination (Sn) and hybridization (Hn). For this purpose, we simulated a genome with 10 linkage groups. In each group, two QTL were simulated. Subsequently, an F2 population was created, followed by four generations of inbreeding (S1 to S4, H1 to H 4, A1, to A4,). Quantitative traits were simulated in three scenarios considering three degrees of dominance (d/a = 0, 0.5 and 1) and two broad sense heritabilities (h2 = 0.30 and 0.70), totaling six genetic architectures. To evaluate prediction reliability, a model (RR-BLUP) was trained in one generation and used to predict the following generations of mating systems. For example, the marker effects estimated in the F2 population were used to estimate the expected genomic breeding value (GEBV) in populations S1 through A4. The squared correlation between the GEBV and the true genetic value were used to measure the reliability of the predictions. Independently of the population used to estimate the marker effect, reliability showed the lowest values in the scenario where d = 1. For any scenario, the use of the multigenerational prediction methodology improved the reliability of GS.
Tactile hypersensitivity and GABA concentration in the sensorimotor cortex of adults with autism

Sensory hypersensitivity is frequently encountered in autism spectrum disorder (ASD). Gamma‐aminobutyric acid (GABA) has been hypothesized to play a role in tactile hypersensitivity. The aim of the present study was twofold. First, as a study showed that children with ASD have decreased GABA concentrations in the sensorimotor cortex, we aimed at determining whether the GABA reduction remained in adults with ASD. For this purpose, we used magnetic resonance spectroscopy to measure GABA concentration in the sensorimotor cortex of neurotypical adults (n = 19) and ASD adults (n = 18). Second, we aimed at characterizing correlations between GABA concentration and tactile hypersensitivity in ASD. GABA concentration in the sensorimotor cortex of adults with ASD was lower than in neurotypical adults (decrease by 17%). Interestingly, GABA concentrations were positively correlated with self‐reported tactile hypersensitivity in adults with ASD (r = 0.50, P = 0.01), but not in neurotypical adults. In addition, GABA concentrations were negatively correlated with the intra‐individual variation during threshold measurement, both in neurotypical adults (r = −0.47, P = 0.04) and in adults with ASD (r = −0.59, P = 0.01). In other words, in both groups, the higher the GABA level, the more precise the tactile sensation. These results highlight the key role of GABA in tactile sensitivity, and suggest that atypical GABA modulation contributes to tactile hypersensitivity in ASD. We discuss the hypothesis that hypersensitivity in ASD could be due to suboptimal predictions about sensations. Autism Research 2019, 12: 562–575. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Clinical and genetic analysis in males with 46,XX disorders of sex development: A reproductive centre experience of 144 cases

To explore the clinical features and assisted reproductive technology (ART) outcomes of 46,XX disorders of sex development (DSD) males, 144 males with 46,XX DSD were recruited in this retrospective study. The baseline information, clinical characteristics and ART outcomes of the participants were collected and analysed. The mean age was 29.06 ± 4.50 years. The mean volumes (95% CI) of left and right testicles were 2.16 (1.82–2.49) ml and 2.16 (1.83–2.49) ml, respectively. Cryptorchidism and/or hypospadias appeared in 19 patients (13.19%). Elevated levels of follicle‐stimulating hormone (FSH) were found in 136 patients (95.10%) and increased luteinising hormone (LH) values were detected in 125 patients (92.59%). Eighty subjects (62.99%) had low testosterone values. Among 86 patients with status of sex‐determining region Y (SRY)—gene and azoospermia factor (AZF) region available, fifteen (17.44%) patients were SRY‐negative and AZF region was absent in every patient without exception. Additionally, fertility achieved in 87 patients through ART using donor spermatozoa. In conclusion, hypergonadotropic hypogonadism appeared as the main presentation of 46,XX DSD males regardless of the SRY status. The available fertility option proved to achieve live birth was limited to ART using donor spermatozoa.
High levels of objectively measured physical activity across adolescence and adulthood among the Pokot pastoralists of Kenya

Levels of physical activity (PA) across the lifespan are important predictors of physical fitness, impacting individual health, and longevity. Individuals living in industrialized societies are often characterized as more sedentary than those who live in small‐scale societies, and this inactivity is generally linked with increased incidence of chronic disease, especially during aging. However, less empirical data exist regarding levels and patterns of PA across the lifespan among small‐scale societies compared with industrialized societies. The goal of this study was to characterize PA among the Pokot pastoralists of rural northern Kenya.
Environmental influences on neuroticism : a story about emotional (in)stability

Een hoog niveau van neuroticisme is een belangrijke risico factor voor zowel psychische als lichamelijke problemen. Bovendien is neuroticisme niet alleen geassocieerd met problemen op het gebied van persoonlijk welbevinden maar ook met substantiele kosten voor de maatschappij. Het is daarom belangrijk om zowel de oorzaken als de gevolgen van neuroticisme beter te begrijpen. Gedrags-genetische studies suggereren dat ongeveer de helft van de verschillen tussen mensen in neuroticisme veroorzaakt wordt door omgevingsinvloeden. In dit proefschrift heb ik onderzocht welke levensgebeurtenissen voorafgaan aan veranderingen in neuroticisme, en hoe lang zulke veranderingen aanhouden. Hiertoe heb ik een aantal longitudinale studies uitgevoerd en de literatuur betreffende veranderingen in neuroticisme in volwassenen samengevat. De resultaten laten zien dat stressvolle levensgebeurtenissen (in het bijzonder sociale stress en conflict), die gekarakteriseerd kunnen worden als onvoorspelbaar, oncontroleerbaar, onverwacht, onwenselijk, of niet passend bij de normale levensloop, vaak worden gevolgd door een langdurige toename in neuroticisme. Echter, positieve levensveranderingen kunnen ook leiden tot een afname van neuroticisme. Daarnaast heb ik de betekenis onderzocht van de relatie tussen neuroticisme en veelvoorkomende psychische problemen, zoals angst, depressie, en middelenmisbruik. De resultaten laten zien dat neuroticisme een belangrijke voorspeller is voor de ontwikkeling van veelvoorkomende psychische problemen, en tot op zekere hoogte gezien kan worden als een maat voor meer milde problemen. De conclusie van dit proefschrift is dat het neuroticisme niveau van mensen mede afhankelijk is van zijn of haar omgeving, gevoelig is voor positieve en negatieve levensgebeurtenissen, consequenties heeft voor psychische gezondheid, en veranderlijker is dan lang werd gedacht.
Comparison of CerviHPV and Hybrid Capture 2 HPV tests for detection of high‐risk HPV infection in cervical swab specimens

Persistent high‐risk human papillomavirus (HR‐HPV) infection is the etiological cause of virtually all cervical cancer cases. HR‐HPV screening achieved with earlier generations of HR‐HPV tests has been instrumental in the prevention and early detection of cervical cancer worldwide. The first FDA‐approved HR‐HPV test, digene Hybrid Capture 2 HPV DNA Test (HC2), has been prominent in these efforts. Newer tests have since been developed to improve upon the capability of HC2 test.
Patients' experience with heart failure treatment and self-care-A qualitative study exploring the burden of treatment.

AIMS AND OBJECTIVES To explore chronic heart failure patients' perceptions of the burden related to treatment and self-care. BACKGROUND Living with chronic heart failure entails following a demanding treatment regimen, with daily self-care, which could make patients vulnerable to experiencing treatment burden. Burden of treatment is defined as the "work" the healthcare system passes on to the patients with respect to self-care at home, and the impact this has on well-being and quality of life. However, the burden of treatment is an emergent framework, and further research exploring burden among heart failure patients is required. DESIGN Qualitative study employing semi-structured interviews and content analysis. The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ). METHODS A sample of 17 heart failure patients recruited from an outpatient clinic in Norway. Interview transcripts were coded in Nvivo 11 and analysed using Malterud's systematic text condensation. RESULTS Two main themes "emotional challenge" and "troublesome self-care" emerged from the analysis. The first theme contained the following subthemes: "a new life situation," "monitoring body signals," "difficult transitions" and "feelings of guilt. " The second theme consisted of the subthemes "poor care coordination," "lack of information and education" and "troublesome medication. " CONCLUSION Heart failure treatment constitutes challenges related both to self-care and to emotional burden. The latter not previously clearly articulated in the concept of burden of treatment. Many patients are struggling emotionally, and this affects their self-care ability in addition to affecting their well-being and quality of life. RELEVANCE TO CLINICAL PRACTICE Nurses are in a strategic position to play a pivotal role in identifying and responding to the emotional burden of treatment in heart failure patients, furthermore to guide and support in discharge planning and in outpatient setting to reduce the patients' emotional distress and fear of failing.