Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of neuroimaging in acute stroke

Background: There is a need for early recognition, diagnosis, and therapy in patients with acute stroke. The most important therapies are thrombolysis or aspirin in hyperacute ischemic stroke and, for secondary prevention, antiplatelet agents, statins, ACE inhibitors (for lowering blood pressure), warfarin, and carotid endarterectomy or stenting. Imaging technology has a crucial role to play in the diagnosis and treatment of stroke. In recent years, significant advances have been made due to the availability of physiological imaging using a variety of techniques, ranging from computerized tomography (CT) to magnetic resonance imaging (MRI), which enable clinicians to define brain anatomy and physiology in greater detail than ever before. Objective: In this article we discuss the imaging techniques currently available for patients with acute stroke, with an emphasis on the utility of these techniques for diagnosis and refining patient selection for early interventions. This is placed in the context of the needs of developing countries. Discussion: Although noncontrast CT (NCCT) remains the most commonly used imaging modality to differentiate between ischemic and hemorrhagic stroke, to identify early CT changes, and to rule out stroke mimics, it is not sensitive enough to identify the infarct core or the mechanism of ischemic stroke. MRI, including magnetic resonance angiography (MRA), is the most useful imaging modality for the evaluation of acute stroke; it provides information about the mechanism as well as the vascular territory of the stroke. MRI also provides complete information about the status of tissue through diffusion-weighted imaging (DWI) and about arterial patency by means of MRA. DWI shows acute lesions within minutes of onset of ischemia, while MRA can evaluate extracranial as well as intracranial vessels Evaluation of the proportion of penumbra vs infarcted tissue is another issue to be considered when instituting thrombolysis, and its clinical usefulness is being assessed in a number of ongoing trials. Penumbral tissue can be identified by perfusion MRI. CT perfusion (CTP) is an emerging alternative, providing similar information about the penumbra and infarct core. A combined approach of NCCT, CT angiography (CTA), and CTP is now being employed at many centers and is known as multimodal CT imaging (MMCT). MMCT provides information about the pathophysiology of acute stroke which is comparable to that provided by MRI, and the technique has the potential to refine patient selection for thrombolysis.
Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.

BACKGROUND & AIMS The role of tobacco smoke in the etiology of inflammatory bowel disease (IBD) is unclear. We investigated interactions between genes and smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and ulcerative colitis (UC) in a case-only study of patients and in mouse models of IBD. METHODS We used 55 Immunochip-wide datasets that included 19,735 IBD cases (10,856 CD cases and 8879 UC cases) of known smoking status. We performed 3 meta-analyses each for CD, UC, and IBD (CD and UC combined), comparing data for never vs ever smokers, never vs current smokers, and never vs former smokers. We studied the effects of exposure to cigarette smoke in Il10-/- and Nod2-/- mice, as well as in Balb/c mice without disruption of these genes (wild-type mice). Mice were exposed to the smoke of 5 cigarettes per day, 5 days a week, for 8 weeks, in a ventilated smoking chamber, or ambient air (controls). Intestines were collected and analyzed histologically and by reverse transcription polymerase chain reaction. RESULTS We identified 64 single nucleotide polymorphisms (SNPs) for which the association between the SNP and IBD were modified by smoking behavior (meta-analysis Wald test P < 5.0 × 10-5; heterogeneity Cochrane Q test P > .05). Twenty of these variants were located within the HLA region at 6p21. Analysis of classical HLA alleles (imputed from SNP genotypes) revealed an interaction with smoking. We replicated the interaction of a variant in NOD2 with current smoking in relation to the risk for CD (frameshift variant fs1007insC; rs5743293). We identified 2 variants in the same genomic region (rs2270368 and rs17221417) that interact with smoking in relation to CD risk. Approximately 45% of the SNPs that interact with smoking were in close vicinity (≤1 Mb) to SNPs previously associated with IBD; many were located near or within genes that regulate mucosal barrier function and immune tolerance. Smoking modified the disease risk of some variants in opposite directions for CD vs UC. Exposure of Interleukin 10 (il10)-deficient mice to cigarette smoke accelerated development of colitis and increased expression of interferon gamma in the small intestine compared to wild-type mice exposed to smoke. NOD2-deficient mice exposed to cigarette smoke developed ileitis, characterized by increased expression of interferon gamma, compared to wild-type mice exposed to smoke. CONCLUSIONS In an analysis of 55 Immunochip-wide datasets, we identified 64 SNPs whose association with risk for IBD is modified by tobacco smoking. Gene-smoking interactions were confirmed in mice with disruption of Il10 and Nod2-variants of these genes have been associated with risk for IBD. Our findings from mice and humans revealed that the effects of smoking on risk for IBD depend on genetic variants.
Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1.

BACKGROUND & AIMS Individuals with Down syndrome have a low risk for many solid tumors, prompting the search for tumor suppressor genes on human chromosome 21 (HSA21). We aimed to identify and explore potential mechanisms of tumor suppressors on HSA21 in hepatocellular carcinoma (HCC). METHODS We compared expression of HSA21 genes in 14 pairs of primary HCC and adjacent noncancer liver tissues using the Affymetrix HG-U133 Plus 2.0 array (Affymetrix, Santa Clara, CA). HCC tissues and adjacent normal liver tissues were collected from 108 patients at a hospital in China for real-time polymerase chain reaction and immunohistochemical analyses; expression levels of regulator of calcineurin 1 (RCAN1) isoform 4 (RCAN1.4) were associated with clinical features. We overexpressed RCAN1.4 from lentiviral vectors in MHCC97H and HCCLM3 cells and knocked expression down using small interfering RNAs in SMMC7721 and Huh7 cells. Cells were analyzed in proliferation, migration, and invasion assays. HCC cells that overexpressed RCAN1.4 or with RCAN1.4 knockdown were injected into livers or tail veins of nude mice; tumor growth and numbers of lung metastases were quantified. We performed bisulfite pyrosequencing and methylation-specific polymerase chain reaction analyses to analyze CpG island methylation. We measured phosphatase activity of calcineurin in HCC cells. RESULTS RCAN1.4 mRNA and protein levels were significantly decreased in primary HCC compared with adjacent noncancer liver tissues. Reduced levels of RCAN1.4 mRNA were significantly associated with advanced tumor stages, poor differentiation, larger tumor size, and vascular invasion. Kaplan-Meier survival analysis showed that patients with HCCs with lower levels of RCAN1.4 mRNA had shorter time of overall survival and time to recurrence than patients whose tumors had high levels of RCAN1.4 mRNA. In HCC cell lines, expression of RCAN1.4 significantly reduced proliferation, migration, and invasive activity. HCC cells that overexpressed RCAN1.4 formed smaller xenograft tumors, with fewer metastases and blood vessels, than control HCC cells. In HCC cells, RCAN1.4 inhibited expression of insulin-like growth factor 1 and vascular endothelial growth factor A by reducing calcineurin activity and blocking nuclear translocation of nuclear factor of activated T cells (NFAT1). HCC cells incubated with the calcineurin inhibitor cyclosporin A had decreased nuclear level of NFAT1. HCC cells had hypermethylation of a CpG island in the 5' regulatory region of RCAN1.4, which reduced its expression. CONCLUSIONS RCAN1.4 is down-regulated in HCC tissues, compared with non-tumor liver tissues. RCAN1.4 prevents cell proliferation, migration, and invasion in vitro; overexpressed RCAN1.4 in HCC cells prevents growth, angiogenesis, and metastases of xenograft tumors by inhibiting calcineurin activity and nuclear translocation of NFAT1.
Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. METHODS We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. RESULTS At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0-1 vs 2-3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91-0.98), and grade 0-2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93-0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2-3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71-0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63-0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity. CONCLUSIONS Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.
Changes in Memory Function and Neuronal Activation Associated with Atorvastatin Therapy

A small number of case studies have reported statin‐induced dementia or memory loss that resolves with cessation of statin therapy. However, such reports have not, to our knowledge, been substantiated by objective measures of changes in brain function during statin treatment and after discontinuation of the drug. We describe a 65‐year‐old man who reported cognitive complaints (memory complaints and mood changes) after taking atorvastatin 10 mg/day for 1 year. He had no history of alcohol consumption, major head trauma, psychiatric problems, or memory impairment. Cognitive testing (Hopkins Verbal Learning Test‐Revised, Brief Visuospatial Memory Test‐Revised, and Wechsler Adult Intelligence Scale, third edition, digit symbol coding and digit span tests) and assessment of neuronal activation using functional magnetic resonance imaging (fMRI) were performed during a working memory task (Sternberg Task) while he was receiving atorvastatin therapy. The patient demonstrated altered neuronal activation (reduced activation of the dorsolateral prefrontal cortex during the encoding task phase and hyperactivation of multiple areas of the prefrontal cortex during the recognition task phase) and reduced performance on the cognitive tests, which was consistent with his cognitive symptoms. These measurements were repeated 2 months after discontinuation of the drug. The patient exhibited improved cognitive test performance and fMRI patterns similar to those expected in a healthy individual. The patient also reported subjective improvement of his cognitive complaints within days of cessation of atorvastatin, which persisted at follow‐up 5 months later (while refraining from any statin use in the interim). To our knowledge, this is the first case report to describe objective cognitive and fMRI findings substantiating statin‐associated effects on the central nervous system, and it provides preliminary evidence that fMRI may be a useful technique for evaluating cognitive function in adults treated with statins.
Differential association between circulating testosterone and infection risk by several viruses in natural cat populations: a behavioural-mediated effect?

SUMMARY Testosterone is involved in the development and expression of physiological, morphological and behavioural traits. High levels are often associated with high infection risk and/or intensity, suggesting a trade-off between sexual traits and immunity. Classically invoked mechanisms are immunological or behavioural, i.e., testosterone increases susceptibility or resistance to parasites via an impact on immunity or modulates behaviours involved in parasite transmission. However, studies report contrasted patterns. Given its modes of action and the diversity of host-parasite interactions, testosterone should not act similarly on all interactions. To reduce host and context diversity, we studied 3 viruses in the same cat population: the aggressively transmitted Feline Immunodeficiency virus (FIV), and the Feline Calicivirus (FCV) and Herpesvirus (FHV) both transmitted during friendly contacts. Testosterone had a strong effect on the probability of being positive to FIV whereas its effect was significantly weaker on FCV and FHV. These findings demonstrate that testosterone can be differentially associated with parasites of the same type (viruses). The difference we observed was consistent with a behavioural-mediated effect (increased aggressiveness), supporting the idea that the testosterone effect on infection risk is at least partially driven by behavioural mechanisms in our system. Further investigations (e.g., individual immunity measures) are required to confirm this hypothesis.
Evaluation and Modification of Low Vision Aids

Many optical appliances provided for 2. the low vision patient are selected from a limited range of aids made available to the profession in Australia through local distributors. There is evidence to support the view that some of these aids have not been designed with the geriatric low vision patient in mind. The versatility and usefulness of some aids can be improved by means of relatively minor modifications. It is suggested that such modifications will provide the practitioner with a freedom to prescribe specifically for the patient. This is preferable to selecting the most suitable aids from a predetermined array followed by counselling the patient on ways of obtaining maximum benefit from them. It is anticipated that such an approach to low vision care will result in a simpler instruction code for the patient and a minimum of after care.
Young children's experiences of living with a parent with bipolar disorder: Understanding the child's perspective

OBJECTIVES To explore the experiences of young children of living with a parent with bipolar disorder (BD) and how this impacts on their emotional well-being. DESIGN Qualitative study using a computer-assisted semi-structured interview, 'In My Shoes' (IMS). METHODS Ten children aged between 4 and 10 years with a parent with BD identified via self-help groups were interviewed about their experience of family life. Thematic analysis was used following transcription. RESULTS Four main themes emerging from thematic analysis were as follows: perception of parents; knowledge and awareness of BD; managing family life with a 'bipolar' parent; and living in a family with BD. Four-year-old children could participate in the IMS interviews and discuss their parent's mood, behaviour, and mental health. Children had candid and insightful discussions about their parent's BD including symptoms and parenting, and could reflect on how having a parent with BD affected them emotionally and practically. Older children were better able to articulate their parent's illness and its impact. CONCLUSIONS This exploratory study represents an important step in examining directly experiences of young children whose parents have BD. Using IMS, it was possible to gather insightful information from children to generate hypotheses and influence service development. Children of all ages had some knowledge and understanding of their parent's illness, describing both positive and negative experiences in the family. Further research to build understanding of children's perspectives and the support they feel they and their family would benefit from would enhance the development of appropriate services and interventions. PRACTITIONER POINTS Using age-appropriate tools, it is possible to elicit the views of young children about their parent's mental health and parenting. Young children have insight into the impact of bipolar disorder in the family on themselves and family members.
Focusing on situation‐specific expectations in major depression as basis for behavioural experiments – Development of the Depressive Expectations Scale

OBJECTIVES Dysfunctional expectations are considered to be core features of various mental disorders. The aim of the study was to develop the Depressive Expectations Scale (DES) as a depression-specific measure for the assessment of dysfunctional expectations. Whereas previous research primarily focused on general cognitions and attitudes, the DES assesses 25 future-directed expectations (originally 75 items) which are situation-specific and falsifiable. DESIGN AND METHODS To evaluate the psychometric properties of the DES, the scale was completed by 175 participants with and without severe depressive symptoms in an online survey. Participants additionally completed the Patient Health Questionnaire modules for depression (PHQ-9) and anxiety (GAD-7). People experiencing depressive symptoms were informed about the study with the help of self-help organizations. RESULTS Reliability analyses indicated excellent internal consistency of the scale. An exploratory factor analyses revealed four factors: social rejection, social support, mood regulation, and ability to perform. The DES sum score strongly correlated with the severity of depressive symptoms. The DES sum score also significantly correlated with symptoms of generalized anxiety. CONCLUSION The DES was shown to have excellent reliability; validity analyses were promising. As the DES items are situation-specific and falsifiable, they can be tested by the individual using behavioural experiments and may therefore facilitate cognitive restructuring. Thus, a structured assessment of patients' expectation with help of the DES can provide a basis for interventions within cognitive-behavioural treatment of depression. PRACTITIONER POINTS Assessing situation-specific expectations in patients experiencing depressive symptoms can provide a basis for the conduction of behavioural experiments to test patients' expectations. For the use of behavioural experiments, therapists should choose those dysfunctional expectations which a patient strongly agrees on. To modify patients' expectations, they should be exposed to situations where the discrepancy between patients' expectations and actual situational outcomes can be maximized. The Depressive Expectations Scale can be completed repeatedly to monitor a patient's progress within cognitive-behavioural treatment.
The phenomenology of self‐critical thinking in people with depression, eating disorders, and in healthy individuals

OBJECTIVES To explore the phenomenology of self-criticism, and the relationship with constructs such as rumination and perfectionism. DESIGN The study followed a three-group (Depression, n = 26; Eating Disorder, n = 26; Non-clinical, n = 26) mixed methods design. METHOD Participants completed a set of questionnaires and were interviewed about the occurrence, impact, and content of self-critical thinking, along with their beliefs about self-criticism. RESULTS Both clinical groups reported more frequent, persistent, and less controllable self-criticism compared to controls, present on average 50-60% of the time. They reported a negative impact on mood, and a moderately severe impact on daily activities. They indicated greater desire to change self-criticism whilst judging it more difficult to reduce. Habitual self-criticism was highly correlated with lower self-esteem, lower self-compassion, greater rumination, and greater negative perfectionism. Compared to those with depression, the eating disorder group reported harsher self-criticism, felt it was more part of their personality, and was more beneficial. CONCLUSIONS The findings highlight the importance of exploring people's beliefs about their self-criticism, and imply that treatment for self-criticism may be more challenging with people with eating disorders than people with depression. PRACTITIONER POINTS This study highlights that self-criticism is common in depression and eating disorders and that some people find this a significant problem in its own right. Careful assessment of self-criticism is recommended when working with these clinical presentations, which should include the perceived positive consequences and desire to change.
Coevolutionary patterns and diversification of avian malaria parasites in African sunbirds (Family Nectariniidae)

SUMMARY The coevolutionary relationships between avian malaria parasites and their hosts influence the host specificity, geographical distribution and pathogenicity of these parasites. However, to understand fine scale coevolutionary host–parasite relationships, robust and widespread sampling from closely related hosts is needed. We thus sought to explore the coevolutionary history of avian Plasmodium and the widespread African sunbirds, family Nectariniidae. These birds are distributed throughout Africa and occupy a variety of habitats. Considering the role that habitat plays in influencing host-specificity and the role that host-specificity plays in coevolutionary relationships, African sunbirds provide an exceptional model system to study the processes that govern the distribution and diversity of avian malaria. Here we evaluated the coevolutionary histories using a multi-gene phylogeny for Nectariniidae and avian Plasmodium found in Nectariniidae. We then assessed the host–parasite biogeography and the structuring of parasite assemblages. We recovered Plasmodium lineages concurrently in East, West, South and Island regions of Africa. However, several Plasmodium lineages were recovered exclusively within one respective region, despite being found in widely distributed hosts. In addition, we inferred the biogeographic history of these parasites and provide evidence supporting a model of biotic diversification in avian Plasmodium of African sunbirds.