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Breast cancer patients are at a particularly high risk of cardiotoxicity from chemotherapy having a detrimental effect on quality-of-life parameters and increasing the risk of mortality. Prognostic biomarkers would allow the management of therapies to mitigate the risks of cardiotoxicity in vulnerable patients and a key potential candidate for such biomarkers are microRNAs (miRNA). miRNAs are post-transcriptional regulators of gene expression which can also be released into the circulatory system and have been associated with the progression of many chronic diseases including many types of cancer. In this review, the evidence for the potential application of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity (CIC) in breast cancer patientsis evaluated and a simple meta-analysis is performed to confirm the replication status of each reported miRNA. Further selection of miRNAs is performed by reviewing the reported associations of each miRNA with other cardiovascular conditions. Based on this research, the most representative panels targeting specific chemotherapy agents and treatment regimens are suggested, that contain several informative miRNAs, including both general markers of cardiac damage as well as those for the specific cancer treatments.

The mutant IDH1 (mIDH1) inhibitor BAY1436032 demonstrated robust activity in preclinical AML models, supporting clinical evaluation. In the current dose-escalation study, BAY1436032 was orally administered to 27 mIDH1 AML subjects across 4 doses ranging from 300 to 1500 mg twice-daily. BAY1436032 exhibited a relatively short half-life and apparent non-linear pharmacokinetics after continuous dosing. Most subjects experienced only partial target inhibition as indicated by plasma R-2HG levels. BAY1436032 was safe and a maximum tolerated dose was not identified. The median treatment duration for all subjects was 3.0 months (0.49–8.5). The overall response rate was 15% (4/27; 1 CRp, 1 PR, 2 MLFS), with responding subjects experiencing a median treatment duration of 6.0 months (3.9–8.5) and robust R-2HG decreases. Thirty percent (8/27) achieved SD, with a median treatment duration of 5.5 months (3.1–7.0). Degree of R-2HG inhibition and clinical benefit did not correlate with dose. Although BAY1436032 was safe and modestly effective as monotherapy, the low overall response rate and incomplete target inhibition achieved at even the highest dose tested do not support further clinical development of this investigational agent in AML.

The effects of azathioprine (AZA) and budesonide (BUD) on mucosal healing and histologic remission of Crohn's disease (CD) are insufficiently studied. In this prospective study we evaluated the comparative effects of AZA and BUD on endoscopic and histologic activity in patients with steroid-dependent Crohn's ileocolitis or proximal colitis who had achieved clinical remission on conventional steroids.MethodsPatients were randomized to AZA (2.0–2.5 mg/kg a day) or BUD (6–9 mg a day) for 1 year. The study protocol included clinical examination, laboratory tests, calculation of the Crohn's Disease Activity Index (CDAI), completion of the Inflammatory Bowel Disease Questionnaire (IBDQ), at baseline and then every 2 months for 1 year. Ileocolonoscopy with regional biopsies was performed at baseline and then at the end of the study to assess mucosal healing and the histologic activity of CD.ResultsThirty-eight patients were randomized to AZA and 39 to BUD. At the end of the study 32 and 25 patients in the AZA and BUD groups, respectively, were in clinical remission (P = 0.07). The Crohn's Disease Endoscopic Index of Severity (CDEIS) score fell significantly only in the AZA group (P < 0.0001). Complete or near complete healing was achieved in 83% of AZA-treated patients compared with only 24% of BUD-treated patients (P < 0.0001). Histologic activity as assessed by an average histology score (AHS) fell significantly only in the AZA group (P < 0.001 versus baseline) and was significantly lower than in the BUD group at the end of the study (P < 0.001). Eight patients in the AZA group were withdrawn for adverse events (n = 6) or relapse of disease compared with 14 patients in the BUD group who were withdrawn for relapse of disease.ConclusionsIn patients with steroid-dependent inflammatory Crohn's ileocolitis or proximal colitis who achieve clinical remission with conventional steroids, a 1-year treatment with AZA was superior to BUD in achieving and maintaining mucosal healing and histologic remission.

Inflammatory bowel diseases (IBDs) are lifelong disorders predominantly present in developed countries. In their pathogenesis, an interaction between genetic and environmental factors is involved. This practice guide, prepared on behalf of the European Society of Pathology and the European Crohn’s and Colitis Organisation, intends to provide a thorough basis for the histological evaluation of resection specimens and biopsy samples from patients with ulcerative colitis or Crohn’s disease. Histopathologically, these diseases are characterised by the extent and the distribution of mucosal architectural abnormality, the cellularity of the lamina propria and the cell types present, but these features frequently overlap. If a definitive diagnosis is not possible, the term indeterminate colitis is used for resection specimens and the term inflammatory bowel disease unclassified for biopsies. Activity of disease is reflected by neutrophil granulocyte infiltration and epithelial damage. The evolution of the histological features that are useful for diagnosis is time- and disease-activity dependent: early disease and long-standing disease show different microscopic aspects. Likewise, the histopathology of childhood-onset IBD is distinctly different from adult-onset IBD. In the differential diagnosis of severe colitis refractory to immunosuppressive therapy, reactivation of latent cytomegalovirus (CMV) infection should be considered and CMV should be tested for in all patients. Finally, patients with longstanding IBD have an increased risk for the development of adenocarcinoma. Dysplasia is the universally used marker of an increased cancer risk, but inter-observer agreement is poor for the categories low-grade dysplasia and indefinite for dysplasia. A diagnosis of dysplasia should not be made by a single pathologist but needs to be confirmed by a pathologist with expertise in gastrointestinal pathology.

To compare the benefits and harms of anti–tumor necrosis factor (TNF)-α and anti-integrin agents as induction and maintenance therapy in adult patients with Crohn’s disease. We searched MEDLINE and the Cochrane Central Register of Controlled Trials from inception through July 2015 for randomized clinical trials in patients with Crohn’s disease who reported response or remission with anti–TNF-α or anti-integrin agents administered as induction and/or maintenance therapy. Data on the study population, interventions, outcome measures, adverse events, and study methods were extracted independently by 2 authors. Among 2503 citations identified, 23 met the eligibility criteria. Random-effects model meta-analyses and network meta-analyses were performed. No statistically significant difference was observed between anti–TNF-α and anti-integrin agents with respect to induction and maintenance of response (odds ratio [OR] = 1.20 [95% CI, 0.73–1.96] from 14 trials and OR = 1.23 [95% CI, 0.50–3.03] from 8 trials, respectively) or remission (OR = 1.13 [95% CI, 0.72–1.76] from 17 trials and OR = 1.18 [95% CI, 0.55–2.50] from 9 trials, respectively). No difference was observed in the indirect comparison of trials that reported results on the subgroup of anti–TNF-α naive patients. The proportions of patients with adverse events, infections, and treatment discontinuations were similar between the agents. Our indirect treatment comparisons did not find a statistically significant difference between anti–TNF-α and anti-integrin agents for induction or maintenance therapy. In the absence of head-to-head comparisons, it remains unclear which patient is more likely to respond better to any of these agents.

Sampling is an important step in the machine learning process because it prioritizes samples that help the model best summarize the important concepts required for the task at hand. The process of determining the best sampling method has been rarely studied in the context of graph neural networks. In this paper, we evaluate multiple sampling methods (i.e., ascending and descending) that sample based off different definitions of centrality (i.e., Voterank, Pagerank, degree) to observe its relation with network topology. We find that no sampling method is superior across all network topologies. Additionally, we find situations where ascending sampling provides better classification scores, showing the strength of weak ties. Two strategies are then created to predict the best sampling method, one that observes the homogeneous connectivity of the nodes, and one that observes the network topology. In both methods, we are able to evaluate the best sampling direction consistently.

The aim of this prospective study was to assess whether the coadministration of azathioprine (AZA) and olsalazine is superior to AZA monotherapy in maintaining remission of steroid-dependent ulcerative colitis (UC). Patients with steroid-dependent UC in remission were randomized to receive AZA alone (2.2 mg/kg) or in combination with olsalazine (0.5 g tid). Remission was defined as steroid withdrawal, an Ulcerative Colitis Clinical Activity Index (UCCAI) score of <2, an Ulcerative Colitis Disease Activity Index (UCDAI) score of 0, and a negative colonoscopy and histology. Patients were followed in the outpatient clinic every month for 2 yr. The study protocol included 1) monthly clinical examination, assessment of UCCAI, hematological and biochemical tests, and compliance with treatment; 2) a sigmoidoscopy and completion of inflammatory bowel disease quality-of-life questionnaire (IBD-Q) and UCDAI every 3 months; and 3) total colonoscopy with biopsies at the end of the first and second year of the trial. Seventy patients were randomized to receive AZA alone (n = 34) or with olsalazine (n = 36). Three patients in each group developed side effects or could not comply with treatment and were withdrawn from the study. Three patients receiving AZA relapsed after the first year of the study and three after the second year of the study (19%). In the combination therapy group four patients relapsed after the first year of study and two after the second year of the study (18%). Relapse rates were not significant whether analyzed by intention-to-treat or per protocol. There were no significant differences between groups in time to relapse or discontinuation of treatment, UCCAI, UCDAI, or IBD-Q scores. However, the number of adverse events and the cost of treatment were significantly higher, whereas compliance with treatment was poorer in the combination therapy. Patients with steroid-dependent UC successfully maintained in remission on AZA are not in need of 5-aminosalicylic acid compounds.

Digital cameras and mobile phones have given people around the world the ability to take a large number of photos and store them on their computers. As these images serve the purpose of storing memories and bringing them to mind in the potentially far future, it is important to also store the impressions a user may have from them. Annotating these images can be a laborious process and the work here presents an application design and functioning implementation, which is openly available now, to ease the effort of this task. It also draws inspiration from interface developments of previous applications such as the Nokia Lifeblog and the Facebook user interface. A different mode of sentiment entry is provided where users interact with slider widgets rather than select a emoticon from a set to offer a more fine grained value. Special attention is made to avoid cognitive strain by avoiding nested tool selections.

Purpose To compare the benefits and harms of anti-tumor necrosis factor (TNF)-α and anti-integrin agents as induction and maintenance therapy in adult patients with Crohn's disease. Methods We searched MEDLINE and the Cochrane Central Register of Controlled Trials from inception through July 2015 for randomized clinical trials in patients with Crohn's disease who reported response or remission with anti-TNF-α or anti-integrin agents administered as induction and/or maintenance therapy. Data on the study population, interventions, outcome measures, adverse events, and study methods were extracted independently by 2 authors. Findings Among 2503 citations identified, 23 met the eligibility criteria. Random-effects model meta-analyses and network meta-analyses were performed. No statistically significant difference was observed between anti-TNF-α and anti-integrin agents with respect to induction and maintenance of response (odds ratio [OR] = 1.20 [95% CI, 0.73-1.96] from 14 trials and OR = 1.23 [95% CI, 0.50-3.03] from 8 trials, respectively) or remission (OR = 1.13 [95% CI, 0.72-1.76] from 17 trials and OR = 1.18 [95% CI, 0.55-2.50] from 9 trials, respectively). No difference was observed in the indirect comparison of trials that reported results on the subgroup of anti-TNF-α naive patients. The proportions of patients with adverse events, infections, and treatment discontinuations were similar between the agents. Implications Our indirect treatment comparisons did not find a statistically significant difference between anti-TNF-α and anti-integrin agents for induction or maintenance therapy. In the absence of head-to-head comparisons, it remains unclear which patient is more likely to respond better to any of these agents.