Miracle-dz/UniFAR-FTUs huggingface dataset:
Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice.

BACKGROUND & AIMS Indian hedgehog (IHH) is an epithelial-derived signal in the intestinal stroma, inducing factors that restrict epithelial proliferation and suppress activation of the immune system. In addition to these rapid effects of IHH signaling, IHH is required to maintain a stromal phenotype in which myofibroblasts and smooth muscle cells predominate. We investigated the role of IHH signaling during development of intestinal neoplasia in mice. METHODS Glioma-associated oncogene (Gli1)-CreERT2 and Patched (Ptch)-lacZ reporter mice were crossed with Apc(Min) mice to generate Gli1CreERT2-Rosa26-ZSGreen-Apc(Min) and Ptch-lacZ-Apc(Min) mice, which were used to identify hedgehog-responsive cells. Cyp1a1Cre-Apc (Apc(HET)) mice, which develop adenomas after administration of β-naphthoflavone, were crossed with mice with conditional disruption of Ihh in the small intestine epithelium. Apc(Min) mice were crossed with mice in which sonic hedgehog (SHH) was overexpressed specifically in the intestinal epithelium. Intestinal tissues were collected and analyzed histologically and by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction. We also analyzed levels of IHH messenger RNA and expression of IHH gene targets in intestinal tissues from patients with familial adenomatous polyposis (n = 18) or sessile serrated adenomas (n = 15) and normal colonic tissue from control patients (n = 12). RESULTS Expression of IHH messenger RNA and its targets were increased in intestinal adenomas from patients and mice compared with control colon tissues. In mice, IHH signaling was exclusively paracrine, from the epithelium to the stroma. Loss of IHH from Apc(HET) mice almost completely blocked adenoma development, and overexpression of SHH increased the number and size of adenomas that developed. Loss of IHH from Apc(HET) mice changed the composition of the adenoma stroma; cells that expressed α-smooth muscle actin or desmin were lost, along with expression of cyclooxygenase-2, and the number of vimentin-positive cells increased. CONCLUSIONS Apc mutant epithelial cells secrete IHH to maintain an intestinal stromal phenotype that is required for adenoma development in mice.
Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis.

BACKGROUND & AIMS There is controversy regarding the best treatment for patients with Crohn's disease because of the lack of direct comparative trials. We compared therapies for induction and maintenance of remission in patients with Crohn's disease, based on direct and indirect evidence. METHODS We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn's disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI). RESULTS Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti-tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2-4.6). CONCLUSIONS Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn's disease.
The developmental proteome of Drosophila melanogaster

Drosophila melanogaster is a widely used genetic model organism in developmental biology. While this model organism has been intensively studied at the RNA level, a comprehensive proteomic study covering the complete life cycle is still missing. Here, we apply label-free quantitative proteomics to explore proteome remodeling across Drosophila’s life cycle, resulting in 7952 proteins, and provide a high temporal-resolved embryogenesis proteome of 5458 proteins. Our proteome data enabled us to monitor isoform-specific expression of 34 genes during development, to identify the pseudogene Cyp9f3Ψ as a protein-coding gene, and to obtain evidence of 268 small proteins. Moreover, the comparison with available transcriptomic data uncovered examples of poor correlation between mRNA and protein, underscoring the importance of proteomics to study developmental progression. Data integration of our embryogenesis proteome with tissue-specific data revealed spatial and temporal information for further functional studies of yet uncharacterized proteins. Overall, our high resolution proteomes provide a powerful resource and can be explored in detail in our interactive web interface.
American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy.

Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina; Division of Infectious Diseases, Brigham & Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology and Hepatology, Yale University School of Medicine, New Haven, Connecticut; and Division of Gastroenterology and Hepatology, Department of Medicine, Case and VA Medical Center, Case Western Reserve University, Cleveland, Ohio
Increase in IkappaB kinase alpha expression suppresses the tumor progression and improves the prognosis for nasopharyngeal carcinoma

Recent studies have suggested that the action of IkappaB kinase alpha (IKKα) as a tumor suppressor is crucial in the development of skin carcinoma, but its role in nasopharyngeal carcinoma (NPC) remains unknown. We examined the IKKα expression in specimens from 157 NPC patients by immunohistochemistry and analyzed the effect of IKKα on prognosis. The functional significance of IKKα expression in NPC cell lines was investigated by IKKα overexpression or downregulation in in vitro studies. The in vitro assays revealed that the IKKα expression was negatively correlated with the invasiveness, migration, and angiogenesis of NPC cells. Overexpression or downregulation of IKKα could significantly repress or enhance the above characteristics, respectively, and these effects were independent of IKKα kinase or EBNA1. In 157 NPC cases, IKKα was differentially expressed in NPC tissues. High expression of IKKα was associated significantly with a high disease‐free survival (DFS; P = 0.002) or overall survival (OS; P = 0.014). Multivariate analyses showed that the IKKα expression was an independent risk factor for DFS (HR, 2.302; P = 0.011) and OS (HR, 3.578; P = 0.006). Our findings indicated that IKKα plays a crucial role as a tumor suppressor that suppresses the invasion, metastasis, and angiogenesis of NPC cells in vitro and correlates with the survival in NPC patients. Therefore, IKKα is not only a novel independent prognostic indicator in NPC, but also targeting IKKα expression may provide a potential therapeutic strategy for NPC. © 2013 Wiley Periodicals, Inc.
University of Birmingham Patients With Acute-on-Chronic Liver Failure Have Increased Numbers of Regulatory Immune Cells Expressing the Receptor Tyrosine Kinase MERTK

Citation for published version (Harvard): Bernsmeier, C, Pop, OT, Singanayagam, A, Triantafyllou, E, Patel, VC, Weston, CJ, Curbishley, S, Sadiq, F, Vergis, N, Khamri, W, Bernal, W, Auzinger, G, Heneghan, M, Ma, Y, Jassem, W, Heaton, ND, Adams, DH, Quaglia, A, Thursz, MR, Wendon, J & Antoniades, CG 2015, 'Patients With Acute-on-Chronic Liver Failure Have Increased Numbers of Regulatory Immune Cells Expressing the Receptor Tyrosine Kinase MERTK', Gastroenterology, vol. 148, no. 3, pp. 603-615. https://doi.org/10.1053/j.gastro. 2014.11. 045
The nuclear matrix protein HNRNPU maintains 3D genome architecture globally in mouse hepatocytes

Eukaryotic chromosomes are folded into higher-order conformations to coordinate genome functions. In addition to long-range chromatin loops, recent chromosome conformation capture (3C)-based studies have indicated higher levels of chromatin structures including compartments and topologically associating domains (TADs), which may serve as units of genome organization and functions. However, the molecular machinery underlying these hierarchically three-dimensional (3D) chromatin architectures remains poorly understood. Via high-throughput assays, including in situ Hi-C, DamID, ChIP-seq, and RNA-seq, we investigated roles of the Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU), a nuclear matrix (NM)-associated protein, in 3D genome organization. Upon the depletion of HNRNPU in mouse hepatocytes, the coverage of lamina-associated domains (LADs) in the genome increases from 53.1% to 68.6%, and a global condensation of chromatin was observed. Furthermore, disruption of HNRNPU leads to compartment switching on 7.5% of the genome, decreases TAD boundary strengths at borders between A (active) and B (inactive) compartments, and reduces chromatin loop intensities. Long-range chromatin interactions between and within compartments or TADs are also significantly remodeled upon HNRNPU depletion. Intriguingly, HNRNPU mainly associates with active chromatin, and 80% of HNRNPU peaks coincide with the binding of CTCF or RAD21. Collectively, we demonstrated that HNRNPU functions as a major factor maintaining 3D chromatin architecture, suggesting important roles of NM-associated proteins in genome organization.
Human-specific features of spatial gene expression and regulation in eight brain regions

Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon, and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific differences. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, whereas the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, and epigenetic modifications were linked to spatial expression differences conserved across species.
Health Food Junkies: Orthorexia Nervosa: Overcoming the Obsession With Healthful Eating

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School nurses’ descriptions of concerns arising during pupils’ health check-ups: A qualitative study

Objective: To describe the concerns and modes of action of Finnish school nurses during pupils’ health check-ups. Methods: Focus group interviews with 17 school nurses were performed in 2011 and again in 2013. Data were analysed using inductive content analysis. Results: School nurses’ concerns were mostly associated with the psychosocial development of pupils and with problems in the family, for example, the loss of a parental role. With regard to physical health, school nurses were particularly concerned with obesity among pupils. The new phenomenon of cyberbullying also caused concern. School nurses were able to identify the causes for their concern at school health check-ups, but they were uncertain regarding how they should act and finding the right mode of action and sufficient multidisciplinary support when pupils had problems. Conclusion: The concern of school nurses at health check-ups was mainly associated with pupils’ health habits, their psychosocial development and family characteristics, and with addressing the need to taking the health behaviours and well-being of the entire family into consideration during health check-ups. Linked-up processes in school health care and multidisciplinary collaboration within schools are of primary importance in supporting the work of nurses and in promoting pupils’ well-being and health.
Verification of an ultrasonographic scoring system in discriminating rheumatoid arthritis from osteoarthritic and normal joints in an Egyptian cohorts

Background The use of musculoskeletal ultrasound in rheumatoid arthritis (RA) has been growing over the last decades mainly to monitor response to treatment and for early detection of erosions. Suggestions to include this technique in the diagnosis of RA have been made, but not yet been implemented (because of the lack of specific sonographic criteria for RA). Objectives To verify the performance of a proposed combined structural and synovial scoring system in differentiating RA from osteoarthritis (OA) and healthy sonographic findings in the small joints of the hand. Patients and methods Twenty RA patients, 20 patients with hand OA, and 10 healthy controls were subjected to musculoskeletal ultrasound of the metacarpophalyngeal and proximal interphalyngeal joints. The novel proposed scoring system was applied characterizing each joint as either RA supported or RA unsupported. Grading of synovitis as mild, moderate, or severe was also performed. In the RA group, disease activity was assessed by Disease Activity Score 28 (DAS28) and anticyclic citrullinated peptide serum levels were measured. Results When one or more RA-supported joints were detected using this scoring system, it had a sensitivity of 100.0% and a specificity of 83.0%, with a diagnostic accuracy of 90.0%, for the diagnosis of RA. If two or more joints were detected, it had a sensitivity of 95.0% and a specificity of 96.7%, with a diagnostic accuracy of 96.0% for the diagnosis of RA. Conclusion The novel suggested combined structural and synovial scoring system showed high performance in differentiating RA from OA and controls.
Counterconditioned fear responses exhibit greater renewal than extinguished fear responses

This series of experiments used rats to compare counterconditioning and extinction of conditioned fear responses (freezing) with respect to the effects of a context shift. In each experiment, a stimulus was paired with shock in context A, extinguished or counterconditioned through pairings with sucrose in context B, and then tested for renewal outside of context B. Counterconditioned fear responses exhibited greater ABA renewal than extinguished fear responses. This result was observed using a between-subjects design (Experiment 1) and a within-subject design in which counterconditioned and extinguished stimuli were equated in all respects other than their signaling of sucrose (Experiment 2). Counterconditioned fear responses also exhibited greater ABC renewal than extinguished fear responses (Experiment 3). This result was observed using a within-subject design in which context C was identical to context B in terms of its associative history, and when counterconditioned and extinguished CSs were tested in compounds matched for their association with both shock and sucrose (Experiment 4). These results are consistent with models which hold that context regulates expression of associations formed in counterconditioning and extinction, and allow the level of regulation to be greater following counterconditioning than extinction, as noted in previous studies.
A UK hospital based multidisciplinary balance clinic run by allied health professionals: first year results.

OBJECTIVE To describe our experience of a new multidisciplinary balance clinic for the management of patients with vestibular disorders, run as a pilot project for 12 months. DESIGN Retrospective review of the outcomes of 194 patients. SUBJECTS All patients were first evaluated at the balance assessment clinic. Subsequently, each case was discussed at the multidisciplinary balance clinic weekly review meeting, and management decisions made. RESULTS The mean waiting time for the balance assessment clinic was 12 weeks (standard deviation six weeks). In total, 74 per cent of patients underwent rehabilitation, 26 per cent were seen in the balance specialist clinic, 15 per cent underwent additional testing, 6 per cent were followed up in adult otology clinics and one patient was listed for surgery. The waiting time for vestibular rehabilitation was reduced from 21 to 15 weeks. Patient satisfaction with the service was encouraging, and no adverse outcomes were recorded. CONCLUSION This multidisciplinary balance clinic, run by allied health professionals, represents an alternative model for the management of patients with balance disorders.
Conditioning- and time-dependent increases in context fear and generalization

A prominent feature of fear memories and anxiety disorders is that they endure across extended periods of time. Here, we examine how the severity of the initial fear experience influences incubation, generalization, and sensitization of contextual fear memories across time. Adult rats were presented with either five, two, one, or zero shocks (1.2 mA, 2 sec) during contextual fear conditioning. Following a recent (1 d) or remote (28 d) retention interval all subjects were returned to the original training context to measure fear memory and/or to a novel context to measure the specificity of fear conditioning. Our results indicate rats that received two or five shocks show an “incubation”-like enhancement of fear between recent and remote retention intervals, while single-shocked animals show stable levels of context fear memory. Moreover, when fear was tested in a novel context, 1 and 2 shocked groups failed to freeze, whereas five shocked rats showed a time-dependent generalization of context memory. Stress enhancement of fear learning to a second round of conditioning was evident in all previously shocked animals. Based on these results, we conclude that the severity or number of foot shocks determines not only the level of fear memory, but also the time-dependent incubation of fear and its generalization across distinct contexts.
Multipole Analysis of Heart Rate Variability as a Predictor of Imminent Ventricular Arrhythmias in ICD Patients

Contemporary implantable cardiac defibrillators (ICD) enable storage of multiple, preepisode R‐R recordings in patients who suffered from ventricular tachyarrhythmia (VTA). Timely prediction of VTA, using heart rate variability (HRV) analysis techniques, may facilitate the implementation of preventive and therapeutic strategies.
Trends in the incidence of Hepatitis B, C and Human Immunodeficiency Virus (HIV) among Blood Donors in a Tertiary Hospital in Nigeria

Background : There have been various claims of reduction in the prevalence of human immunodeficiency virus and other transfusion transmissible viruses in the general population following various interventions including public awareness campaigns, provision of facilities for voluntary counselling and testing, programmes for prevention of mother to child transmission and provision of antiretroviral drugs to people living with HIV/AIDS. How has these interventions affected the incidence of the transfusion transmissible viruses among blood donors? This study aims at identifying the trends in the incidence of seropositivity of hepatitis B, C and human immunodeficiency virus among blood donors in a tertiary hospital in Nigeria. Method : Blood bank records of intending blood donors who were screened for hepatitis B, C and anti HIV antibodies for the years 2004 to 2008 were retrieved and analysed. Results : A total of fifty five thousand four hundred and seventy five (55,475) intending blood donors were screened for Hepatitis B surface antigen and antibodies to HCV and HIV. HBsAg screening constituted the most frequently screened for evidence of transfusion transmissible viruses (n=26,559; 47.9%), closely followed by HIV (n=15,569; 28.0%) and the least is HCV (n=13,347; 24.1%). HBsAg seropositivity has the highest incidence for all the years under review with mean incidence of 14.9%. This is followed by HIV seropositivity with mean incidence of 6.4% and the least is HCV with mean incidence of 6.1%. Conclusion : The trend in the incidence of seropositivity of hepatitis B and HIV among blood donors is fluctuating without any sign of sustained decline. Only hepatitis C seropositivity shows a downward trend. More intervention in public awareness campaigns on the need to abstain from high risk behaviours and improvement in screening facilities are required.