GBDTMO: as new option for early-stage breast cancer detection and classification using machine learning

Breast cancer is the second leading cause of disease death in women, after lung and bronchus cancer. According to measurements, mammography misses breast cancer in 10% to 15% of cases for women aged 50 to 69 years. In the current study, we used the Wisconsin breast cancer dataset to develop a two-stage model for breast cancer diagnosis. The main goal of this study effort is to effectively carry out feature selection and classification tasks. Gradient Boosting Decision Tree-based Mayfly Optimisation (GBDTMO), an innovative and efficient breast cancer diagnostic machine learning system, is provided. In the second stage, we employ a Mayfly search to determine which subset of traits is the best. Two more well-known datasets on breast cancer, the ICCR and the Cancer Corpus, were also compared for classification accuracy. The accuracy of the suggested GBDTMO model was higher than that of the existing GBDT and Practical Federated Gradient Boosting Decision Tree (PFGBDT), which had accuracy values of 93.25% and 94.25%, respectively. Similarly, the recall, F-measure, and ROC area values were 98.52%, 97.52%, and 96.32%, respectively. Furthermore, it demonstrated a lower RMSE of 0.98 than the existing GBDT and PFGBDT

Modulation of the Intestinal Microbiota Alters Colitis-Associated Colorectal Cancer Susceptibility

It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) collectively referred to as inflammatory bowel disease (IBD). Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC). However, the impact of the microbiota on the development of colitis-associated cancer (CAC) remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM)-exposed, conventionalized-Il10−/− mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62%) of AOM-Il10−/− mice developed colon tumors compared to only 3/15 (20%) of AOM- wild-type (WT) mice. Conventionalized AOM-Il10−/− mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10−/− mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10−/− mice. Germ-free AOM-treated Il10−/− mice showed normal colon histology and were devoid of tumors. Il10−/−; Myd88−/− mice treated with AOM displayed reduced expression of Il12p40 and Tnfα mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma

Razvoj i optimizacija sustava za isporuku metoprolol sukcinata sa zadržavanjem u želucu

Metoprolol succinate (MS) gastroretentive (GR) controlled release system was formulated to increase gastric residence time leading to improved drug bioavailability. Box-Behnken model was followed using novel combinations of sodium alginate (SA), sodium carboxymethylcellulose (NaCMC), magnesium alumino metasilicate (MAS) as independent variables. Floating lag time (Flag), t25, t50, t75, diffusion exponent as dependent variables revealed that the amount of SA, NaCMC and MAS have a significant effect (p < 0.05) on t25, t50, t75 and Flag. MSGR tablets were prepared and evaluated for mass, thickness, hardness, friability, drug content and floating property. Tablets were studied for dissolution for 24 h and exhibited controlled release of MS with floating for 16 h. The release profile of the optimized batch MS01 fitted first-order kinetics (R2 = 0.9868, n = 0.543), indicating non-Fickian diffusion or anomalous transport by diffusion and swelling.U radu je opisan razvoj sustava za isporuku metoprolol sukcinata (MS) s kontroliranim oslobađanjem i produljenim vremenom zadržavanja u želucu (GR), u svrhu poboljšanja bioraspoloživosti. Primijenjen je Box-Behnkenov model, a kao zavisne varijable izabrane su nove kombinacije natrijevog alginata (SA), natrijeve soli karboksimetilceluloze (NaCMC) i magnezijevog aluminometasilikata (MAS). Vrijeme plutanja (Flag), t25, t50, t75 i difuzijski eksponent kao zavisne varijable otkrili su da količina SA, NaCMC i MAS ima značajan učinak (p < 0,05) na t25, t50, t75 i Flag. Pripravljenim tabletama određena je masa, debljina, tvrdoća, lomljivost, sadržaj ljekovite tvari i sposobnost plutanja. Oslobađanje MS praćeno je 24 h. Rezultati pokazuju da je oslobađanje kontrolirano, a vrijeme plutanja 16 h. Oslobađanje iz optimiranog pripravka MS01 slijedi kinetiku prvog reda (R2 = 0,9868, n = 0,543), što ukazuje na difuziju koja ne slijedi Fickov zakon već anomalni transport difuzijom i bubrenjem

Severe de novo Ulcerative Colitis following Ixekizumab Therapy

Ixekizumab is a selective monoclonal antibody targeting interleukin-17A, approved for the treatment of chronic plaque psoriasis. It has rarely been associated with inflammatory bowel disease (IBD) in randomized trials only. We report a unique case of severe new-onset ulcerative colitis in a young male complicated by cytomegalovirus infection who was on ixekizumab therapy for plaque psoriasis. We recommend that clinicians should exercise caution before prescribing ixekizumab as it seems to induce and exacerbate IBD

Activation of NF-κB after chronic ethanol intake and haemorrhagic shock/resuscitation in mice: NF-κB after chronic ethanol and H/R

Chronic ethanol abuse and haemorrhagic shock are major causes of global mortality and, separately, induce profound hepato- and immune-toxic effects via activation of NF-κB. Here, we assessed the effects of chronic ethanol intake upon the pathophysiological derangements after haemorrhagic shock with subsequent resuscitation (H/R), with particular attention to the contribution of NF-κB

The Link between the Baryonic Mass Distribution and the Rotation Curve Shape

The observed rotation curves of disc galaxies, ranging from late-type dwarf galaxies to early-type spirals, can be fit remarkably well simply by scaling up the contributions of the stellar and HI discs. This `baryonic scaling model' can explain the full breadth of observed rotation curves with only two free parameters. For a small fraction of galaxies, in particular early-type spiral galaxies, HI scaling appears to fail in the outer parts, possibly due to observational effects or ionization of the HI. The overall success of the baryonic scaling model suggests that the well-known global coupling between the baryonic mass of a galaxy and its rotation velocity (known as the baryonic Tully-Fisher relation), applies at a more local level as well, and it seems to imply a link between the baryonic mass distribution and the distribution of total mass (including dark matter).Comment: 10 pages, accepted for publication in MNRA

Modulation of the Intestinal Microbiota Alters Colitis-Associated Colorectal Cancer Susceptibility

It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) collectively referred to as inflammatory bowel disease (IBD). Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC). However, the impact of the microbiota on the development of colitis-associated cancer (CAC) remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM)-exposed, conventionalized-Il10−/− mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62%) of AOM-Il10−/− mice developed colon tumors compared to only 3/15 (20%) of AOM- wild-type (WT) mice. Conventionalized AOM-Il10−/− mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10−/− mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10−/− mice. Germ-free AOM-treated Il10−/− mice showed normal colon histology and were devoid of tumors. Il10−/−; Myd88−/− mice treated with AOM displayed reduced expression of Il12p40 and Tnfα mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma

Solid state image sensor research, phase 2

Solid state image sensor arra

GSK3β inhibition blocks melanoma cell/host interactions by downregulating N-cadherin expression and decreasing FAK phosphorylation.

This study addresses the role of glycogen synthase kinase (GSK)-3β signaling in the tumorigenic behavior of melanoma. Immunohistochemical staining revealed GSK3β to be focally expressed in the invasive portions of 12 and 33% of primary and metastatic melanomas, respectively. GSK3 inhibitors and small interfering RNA (siRNA) knockdown of GSK3β were found to inhibit the motile behavior of melanoma cells in scratch wound, three-dimensional collagen-implanted spheroid, and modified Boyden chamber assays. Functionally, inhibition of GSK3β signaling was found to suppress N-cadherin expression at the messenger RNA and protein levels, and was associated with decreased expression of the transcription factor Slug. Pharmacological and genetic ablation of GSK3β signaling inhibited the adhesion of melanoma cells to both endothelial cells and fibroblasts and prevented transendothelial migration, an effect rescued by the forced overexpression of N-cadherin. A further role for GSK3β signaling in invasion was suggested by the ability of GSK3β inhibitors and siRNA knockdown to block phosphorylation of focal adhesion kinase (FAK) and increase the size of focal adhesions. In summary, we have, to our knowledge, demonstrated a previously unreported role for GSK3β in modulating the motile and invasive behavior of melanoma cells through N-cadherin and FAK. These studies suggest the potential therapeutic utility of inhibiting GSK3β in defined subsets of melanoma