tbuckley/cabot-search huggingface dataset:
Identification and genomic characterization of single disseminated progenitor cells of bone metastasis in prostate cancer
Authors: Bernhard Polzer, Dorothea Weckermann, Hans Arnholdt, Sonja Offner, Christoph A. Klein
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4303 

The detection of cytokeratin 8, 18, and 19 (CK)-positive cells in bone marrow of carcinoma patients correlates with poor prognosis for various tumors. Interestingly, although bone is by far the preferred site of metastases in prostate cancer the prognostic impact of CK-positive cells in prostate cancer, despite being consistently observed, is less significant than in breast cancer. Therefore we investigated whether disseminated prostate cancer cells downregulate cytokeratins 8,18, and 19 and can be detected by other markers, e.g. epithelial adhesion molecule (EpCAM). We isolated positive cells from both groups and further characterized their genomic organization. We screened 660 bone marrow samples of prostate cancer patients using mAb A45/B-B3 directed against cytokeratin 8, 18, and 19 and 328 samples with an antibody directed against EpCAM. Additional 80 samples were tested by doublestaining against both epithelial markers. DNA isolated from 83 CK-positive and 52 EpCAM-positive single cells, as well as from 40 areas of 27 primary tumors was analyzed by comparative genomic hybridization (CGH) following whole genome amplification. The analysis of single disseminated tumor cells from bone marrow by CGH clearly demonstrated that both CK+ and EpCAM+ cells are tumor cells. We observed a striking genomic heterogeneity between disseminated tumor cells from different patients without manifest metastases (clinical stage M0) and between individual tumor cells from the same patient. On the other hand, the genomes of disseminated tumor cells from patients with metastatic disease (M1) were highly similar and specific chromosomal aberrations apparently were selected during metastatic progression. Genomic heterogeneity was also evident between several microdissected areas from individual primary tumors as well as between primary tumors and their disseminated cancer cells. Furthermore, CGH defined genomic aberrations characteristic for CK+ and EpCAM+ cells, respectively, and double staining against both epithelial markers identified three genetically divergent subsets of disseminated tumor cells. These findings indicate an unexpected diversity of early-disseminated cancer cells displaying different phenotypes and possibly divergent metastatic potential.
Restenosis, reocclusion and adverse cardiovascular events after successful balloon angioplasty of occluded versus nonoccluded coronary arteries
Authors: Peter B. Berger, David R. Holmes, E. Magnus Ohman, Mary Ann O'Hanesian, Joseph G. Murphy, Robert S. Schwartz, Patrick W. Serruys, David P. Faxon
Journal: Journal of the American College of Cardiology (1996)
FAMCS: Finding All Maximal Common Substructures in Proteins
Authors: Zhen Yao, Juan Xiao, Anthony K.H. Tung, Wing Kin Sung
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract Finding the common substructures shared by two proteins is considered as one of the central issues in computational biology because of its usefulness in understanding the structure-function relationship and application in drug and vaccine design. In this paper, we propose a novel algorithm called FAMCS (Finding All Maximal Common Substructures) for the common substructure identification problem. Our method works initially at the protein secondary structural element (SSE) level and starts with the identification of all structurally similar SSE pairs. These SSE pairs are then merged into sets using a modified Apriori algorithm, which will test the similarity of various sets of SSE pairs incrementally until all the maximal sets of SSE pairs that deemed to be similar are found. The maximal common substructures of the two proteins will be formed from these maximal sets. A refinement algorithm is also proposed to fine tune the alignment from the SSE level to the residue level. Comparison of FAMCS with other methods on various proteins shows that FAMCS can address all four requirements and infer interesting biological discoveries.
CD14+ cell-derived IL-29 modulates proinflammatory cytokine production in patients with allergic airway inflammation
Authors: S. He, T. Li, H. Chen, W. Ma, Q. Yao, H. Yang, H. Wang, F. Wang, C. Zhao, P. Yang
Journal: Allergy (2010)

Interleukin (IL)-29 is a newly described cytokine that has anti-viral activity, induces tumor cell death and regulates immune function. Whether it plays a role in immune disorders is unclear. This study aims to examine the role of IL-29 in the modulation of immune response under allergic environment. A group of patients with allergic asthma or/and allergic rhinitis was recruited to this study. Serum samples were collected from the patients in both in-season and out-season; the serum levels of IL-29 were determined by enzyme-linked immunoassay. Cell types of IL-29-producing cells in upper airway mucosa were identified with immune staining and examined by immunohistochemistry and flow cytometry. High serum levels of IL-29 were detected in patients with allergic asthma in in-season, but not in out-season. The majority of IL-29(+) cells in upper airway tissue were CD14(+) cells. Exposure to specific antigens triggered the release of IL-4 from antigen-specific CD4(+) T cells; the released IL-4 activated CD14(+) cells to release IL-29; the released IL-29 further triggered the release of IL-6 and tumor necrosis factor from CD4(+) T cells. Interleukin-29 is involved in the pathogenesis of allergic inflammation via modulating immune cells' function to release proinflammatory cytokines.
Post-transcriptional Modifications Contribute to the Upregulation of Cyclin D2 in Multiple Myeloma
Authors: Irena Misiewicz-Krzeminska, María E. Sarasquete, Carolina Vicente-Dueñas, Patryk Krzeminski, Katarzyna Wiktorska, Luis Antonio Corchete, Dalia Quwaider, Elizabeta A. Rojas, Rocío Corral, Ana A. Martín, Fernando Escalante, Abelardo Bárez, Juan Luis García, Isidro Sánchez-García, Ramón García-Sanz, Jesús F. San Miguel, Norma C. Gutiérrez
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Dysregulation of one of the three D-cyclin genes has been observed in virtually all multiple myeloma tumors. The mechanisms by which CCND2 is upregulated in a set of multiple myeloma are not completely deciphered. We investigated the role of post-transcriptional regulation through the interaction between miRNAs and their binding sites at 3′UTR in CCND2 overexpression in multiple myeloma. Experimental Design: Eleven myeloma cell lines and 45 primary myeloma samples were included in the study. Interactions between miRNAs deregulated in multiple myeloma and mRNA targets were analyzed by 3′UTR-luciferase plasmid assay. The presence of CCND2 mRNA isoforms different in length was explored using qRT-PCR, Northern blot, mRNA FISH, and 3′ rapid amplification of cDNA ends (RACE)-PCR. Results: We detected the presence of short CCND2 mRNA, both in the multiple myeloma cell lines and primary cells. The results obtained by 3′RACE experiments revealed that changes in CCND2 3′UTR length are explained by alternative polyadenylation. The luciferase assays using plasmids harboring the truncated CCND2 mRNA strongly confirmed the loss of miRNA sites in the shorter CCND2 mRNA isoform. Those multiple myelomas with greater abundance of the shorter 3′UTR isoform were associated with significant higher level of total CCND2 mRNA expression. Furthermore, functional analysis showed significant CCND2 mRNA shortening after CCND1 silencing and an increased relative expression of longer isoform after CCND1 and CCND3 overexpression, suggesting that cyclin D1 and D3 could regulate CCND2 levels through modifications in polyadenylation-cleavage reaction. Conclusions: Overall, these results highlight the impact of CCND2 3′UTR shortening on miRNA-dependent regulation of CCND2 in multiple myeloma. Clin Cancer Res; 22(1); 207–17. ©2015 AACR.
Rory Louis Carson
Authors: K. Carson
Journal: BMJ (2015)

<h3>Abstract</h3> Predicting mutation-induced changes in protein thermodynamic stability (ΔΔG) is of great interest in protein engineering, variant interpretation, and drug discovery. We introduce ThermoNet, a deep, 3D-convolutional neural network designed for structure-based prediction of the change in protein thermostability upon point mutation. To naturally leverage the image-processing power inherent in convolutional neural networks, we treat protein structures as if they were multi-channel 3D images. In particular, the inputs to ThermoNet are multi-channel voxel grids based on biophysical properties derived from raw atom coordinates; thus, the interpretability of its resulting predictions is improved compared to machine-learning approaches that take heterogeneous representations of predictive features as inputs. ThermoNet is trained with a data set balanced with direct and reverse mutations generated by symmetry-based data augmentation. It demonstrates improved performance compared to fifteen previously developed computational methods on a widely used blind test set. Unlike all other methods that exhibit a strong bias towards predicting destabilization, ThermoNet accurately predicts the effects of both stabilizing and destabilizing mutations. Finally, we demonstrate the practical utility of ThermoNet in predicting the ΔΔG landscape for two clinically relevant proteins, p53 and myoglobin, and all ClinVar missense variants. These predictions indicate that 85.1% of benign variants have effects on protein stability that are in the range expected to be neutral and that pathogenic variants are almost equally likely to be destabilizing as stabilizing (56.6% vs 43.4%, respectively). Overall, our results suggest that 3D convolutional neural networks can model the complex, non-linear interactions perturbed by mutations, directly from biophysical properties of atoms.
Cognitive behaviour therapy for the chronic fatigue syndrome
Authors: S A Chilton
Journal: BMJ (1996)

Cognitive behaviour therapy for the chronic fatigue syndrome Evening primrose oil and magnesium have been shown to be effective EDITOR,-In their paper on cognitive behaviour therapy for -the chronic fatigue syndrome Michael Sharpe and colleagues state that many pharmacological treatments have been suggested but none are of proved value.'Last year Lewith stated that the only two treatments that had been properly evaluated were evening primrose oil and magnesium by injection.2Intramuscular magnesium supplements have been given to patients with low red cell magnesium in a double blind placebo controlled trial; myalgia and fatigue improved in about 70% of subjects.3Evening primrose oil has been used to treat myalgic encephalomyelitis and is the only other treat- ment that has been adequately tested in a controlled trial.High doses in randomised controlled trials have been shown to have a significant effect in 70-80% of patients with myalgic encephalomyelitis or the chronic fatigue syndrome.4I would be interested to hear Sharpe and colleagues' comments about these papers.
Successful treatment of facial blushing by endoscopic transthoracic sympathicotomy
Authors: None Drott, None Claes, None Olsson-Rex, None Dalman, None FahlÉN, None GÖthberg
Journal: British Journal of Dermatology (1998)

Facial blushing is one of the cardinal symptoms of social phobia and has a strong negative impact on the quality of life. Traditional therapeutic options are psychotherapy and pharmacological treatment. The results of these treatments on facial blushing are poorly documented. To investigate whether endoscopic bilateral transection of the upper thoracic sympathetic chain is efficient in the treatment of facial blushing, 244 consecutive patients were treated with bilateral endoscopic transthoracic sympathicotomy (ETS). The results were evaluated by questionnaire and symptoms assessed with visual analogue scales (0–10). There was no mortality nor conversion to open surgery. No Horner's syndrome occurred. Two patients with postoperative pneumothorax were treated with intercostal drainage and one small pulmonary embolus was detected. The questionnaire was answered by 219 patients (90%) a mean (± SEM) of 8 months (± 9 days) after surgery. Facial blushing (mean ± SEM) was reduced from 8.7 ± 0.1 to 2.2 ± 0.2, P < 0.0001, by the operation. Heart palpitations in stressful situations were also reduced (3.7 ± 0.3 to 1.3 ± 0.1, P < 0.0001). The quality of life was substantially improved. The main side-effect was redistribution of sweating from the upper to the lower part of the body. Increased sweating of the trunk occurred in 75% of the patients. Overall, 85% of the patients were satisfied with the result and 15% were to some degree dissatisfied, mainly due to insufficient effect, but only four patients (2%) regretted the operation. As this is an open study, the results must be viewed with caution. ETS, however, appears to be an efficient, safe and minimally invasive surgical method for the treatment of facial blushing.
Role of traditional birth attendants in preventing perinatal transmission of HIV Commentary: Involving traditional birth attendants in prevention of HIV transmission needs careful consideration
Authors: M. Bulterys
Journal: BMJ (2002)

# Role of traditional birth attendants in preventing perinatal transmission of HIV {#article-title-2}

Every year a million women infected with HIV deliver babies without professional help. Marc Bulterys and colleagues suggest here that traditional birth attendants could be involved in preventing perinatal transmission of HIV by offering services such as HIV testing and counselling and short courses of antiretroviral drugs. A research doctor in the Gambia comments on this suggestion

In many poor parts of the world, the HIV and AIDS epidemic has eroded hard won gains in the survival of infants and children.1 In eastern and southern Africa, infant mortality is one third to two thirds higher than it would have been in the absence of HIV and AIDS, and child mortality continues to rise, leading to a dramatic reduction in life expectancy. 1 2

In rich nations, rates of perinatal transmission of HIV less than 2% are now reported because of the use of combinations of antiretroviral drugs, elective caesarean section, and avoidance of breastfeeding.3–5 Transmission rates of 5% or lower may be achievable in middle income countries and some urban areas of the developing world with the use of short courses of combinations of antiretroviral drugs, appropriate infant feeding choices, and possibly elective caesarean delivery. 1 6 However, being able to extend the benefits of these recent advances to most women infected with HIV is a tremendous challenge, particularly in rural communities, in which more than two thirds of the population of sub-Saharan Africa lives.

The simplicity and low cost of nevirapine's single dose regimen 7 8 suggest that this highly efficacious drug might be very useful in rural settings. Obstacles to its use—including weak, underlying healthcare infrastructures9 and low rates of offering and uptake of voluntary counselling and testing—will be magnified in rural areas. 1 10 As global efforts to prevent perinatal transmission of …
Interpretation of passive respiratory mechanics in infants: Should we normalise by body weight?
Authors: Ah-Fong Hoo, Sooky Lum, Angie Wade, Janet Stocks
Journal: European Respiratory Journal (2011)

Introduction:  Tidal volume ( V  T ) and respiratory compliance ( C rs) are commonly normalised for body weight; whether this is appropriate beyond the neonatal period or in weight restricted children remains unclear.   Aim:  To examine the relationship between  V  T ,  C rs and growth in healthy infants.   Methods:  The Jaeger BabyBody (v4.6) was used to assess lung function (LF) in healthy, sedated term Caucasian infants.   Results:  Technically satisfactory  V  T  and  C rs from 140 infants [median (range) age: 38 (3-105) w] were available on 192 & 84 occasions respectively (Table).  The average relationship between  V  T  or  C rs and weight was constant over time but between-subject variability increased with growth (Fig. 1ab light-for-age babies had higher values than those who were heavier. This again may lead to misdiagnosis especially in those with impaired growth (eg, CF).   Conclusions:  Reporting infant LF/kg body weight is inappropriate. Equipment-specific regression equations are needed to avoid misinterpretation; for this a larger dataset is required. We would welcome contributions of similar data from other centres.
Exosomal microRNAs in the serum are potential real-time biomarkers for allergic inflammation in the airway of mice
Authors: Shuichiro Maruoka, Yasuhiro Gon, Sotaro Shikano, Yoshitaka Shintani, Daisuke Koyama, Tadataka Sekiyama, Hisato Hiranuma, Toshio Inoue, Ikuko Takeshita, Eriko Tsuboi, Kaori Soda, Shu Hashimoto
Journal: European Respiratory Journal (2014)

Background  MicroRNAs (miRNAs) have been reported as useful therapeutic and diagnostic targets for patients with asthma. Even ribonucleases (RNase) are present throughout the human body, miRNAs is stably exist in body fluids because they are contained in exosomes. However, little is known regarding which exosomal miRNAs in the serum are suitable for the real-time monitoring of allergic inflammation in the airway. We therefore investigated miRNA expression profiles of serum exosomes and lung tissues isolated from house dust mite (HDM)-exposed mice.  Methods  We sensitized and challenged mice with HDM or saline as control on day1, 8 and 15. On day 18, we collected lung tissues and serum from HDM- or saline- exposed mice. Total RNAs were extracted from lung tissues using total RNA isolation kit and serum exosomes using exosomal RNA purification kit. Then we performed miRNA array analysis to identify exosomal miRNAs in the serum, which might be involved in ongoing allergic airway inflammation in the airway of mice. Data analysis was performed using GeneSpring software. Gene network analysis was performed using Ingenuity Pathways Analysis. We also validated gene expression of candidate miRNAs using real-time PCR.  Results  We identified 100 HDM-inducible miRNAs in serum exosomes and 175 miRNAs in lung tissues. 5 up-regulated miRNAs or 5 down-regulated miRNAs were found to be common in both serum exosomes and lung tissues from HDM-sensitized mice.  Conclusions  Our data suggest that exosomal miRNAs in the serum we identified might be new diagnostic biomarkers or therapeutic targets for allergic inflammation in the airway.
Phase I study of the combination of fludarabine, mitoxantrone, and dexamethasone in low-grade lymphoma.
Authors: P McLaughlin, F B Hagemeister, F Swan, F Cabanillas, O Pate, J E Romaguera, M A Rodriguez, J R Redman, M Keating
Journal: Journal of Clinical Oncology (1994)

Fludarabine is an active agent for patients with low-grade lymphoma (LGL) but has mainly been used as a single agent. This trial was designed to define the maximum-tolerated dose (MTD) of a combination of fludarabine, mitoxantrone, and dexamethasone (FND), to identify the toxicities of these agents in combination, and to make preliminary observations about the efficacy of this combination.Twenty-one patients with recurrent LGL or follicular large-cell lymphoma were treated, in cohorts of three, at stepwise escalating doses. Patients were required to have adequate marrow function and normal renal, hepatic, and cardiac function.The MTD of the combination was found to be as follows: fludarabine, 25 mg/m2/d (days 1 to 3); mitoxantrone, 10 mg/m2 (day 1); and dexamethasone, 20 mg/d (days 1 to 5). Each course was administered monthly, and up to eight courses were given. Dose-limiting toxicities were neutropenia and infections. Thrombocytopenia was modest. Nonhematologic toxicity was very modest. Responses were seen at every dose level. The overall response rate was 71%, with a 43% complete remission (CR) rate. The median duration of CR was 18 months (with follow-up duration from 13 to 28+ months).FND was well tolerated in this population. While our primary aim was to define the MTD, our preliminary observations on the efficacy of the regimen were favorable. The overall response rate was high, there was a high fraction of CRs, and our early impression is that these responses are durable.
Cancer risk in asthmatic subjects selected from hospital discharge registry
Authors: B Kallen, J Gunnarskog, TB Conradson
Journal: European Respiratory Journal (1993)

We wanted to study cancer risk in asthmatic subjects. With the use of central health registries, a cohort of 64,346 patients, treated in hospital with an asthma diagnosis, was followed with respect to cancer development. The observed numbers of different types of cancer were compared with the expected numbers, estimated from population data, with consideration taken to patient age, sex, survival, and the year of diagnosis. In general, a marked reduction of cancer incidence (2 out of 3 of the expected numbers) was found, with the exception of two cancer types: cancer of the respiratory tract and cancer of endocrine glands. A more noticeable reduction in cancer risk was seen for multiple myeloma, malignant melanoma, mammary cancer, uterine body cancer, and stomach cancer. The causes of this "protective effect" are not indicated by the present analysis, and need further study.
Imaging findings for intravascular large B-cell lymphoma of the liver
Authors: Jungmin Bae, Hyo Keun Lim, Ha Young Park
Journal: Clinical and Molecular Hepatology (2015)

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma that most commonly involves the central nervous system and skin. To our knowledge, no state-of-the art imaging findings have been reported for hepatic IVLBCL in the English literature. We report the first case of hepatic involvement of IVLBCL along with a literature review. Keywords: Liver neoplasm; Lymphoma; Diagnosis
The utility of vibration response imaging for calculation of ppoFEV1 and ppoDL,CO in patients with lung cancer referred for resection - The influence of coexisting COPD
Authors: Blagoi Marinov, Anastas Chapkanov, Miroslava Todorova, Georgi Paskalev, Stefan Kostianev
Journal: European Respiratory Journal (2013)

Background: Patients with operable lung cancer often have coexisting obstructive lung disease that reduces their ability to endure additional loss of pulmonary function.  Aim: To investigate whether coexisting COPD influences the calculation of predicted postoperative (ppo) values by means of vibration response imaging (VRI) in patients with lung cancer referred for resection.  Patients and methods: Seventeen patients with non small cell lung cancer (mean±SD age=60.6±8.6 years) referred for anatomical lung resection were studied. They underwent comprehensive spirometry testing, diffusion measurements (MasterScreen Diffusion, E. Jaeger, Germany) and vibration response imaging (VRIxp, DeepBreeze, Israel) before and 30 days after the resection. The calculation of the ppo values was carried out with proprietary software O-Plan.  Results: Thirteen lobectomies and 4 pneumonectomies were performed in the studied population (12 males/5 females). Strong correlations were found between the ppoFEV1 (% pred) and ppoD L,CO  (% pred) values predicted with VRIxp O-Plan and the actually measured values 30 days postoperatively (r=0.794; p L,CO  was similar in both groups (r=0.919; p  Conclusion: VRI correctly predicts postoperative values for FEV1 and D L,CO . In patients with COPD the calculation of ppoFEV1 is more accurate compared to non-COPD group.