LLukas22/scidocs huggingface dataset:
Oxaliplatin/capecitabine vs oxaliplatin/infusional 5-FU in advanced colorectal cancer: the MRC COIN trial

Background:COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC).Methods:Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment.Results:In total, 64% of 2397 patients received OxCap(±cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (±cetuximab) was associated with more mucositis and infection whereas OxCap(±cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50–80 ml min−1 on OxCap(±cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function.Conclusions:Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50–80 ml min−1 on both regimens require close toxicity monitoring.
Plasma ESR 1 Mutations and the Treatment of Estrogen Receptor – Positive Advanced Breast Cancer

Purpose ESR1mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer.We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis,weassessedESR1mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus ExemestaneWith or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients withESR1mutationshad improvedprogression-freesurvival (PFS) after taking fulvestrant (n=45) compared with exemestane (n=18; hazard ratio [HR], 0.52; 95%CI, 0.30 to 0.92;P= .02),whereas patientswithwildtype ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3,ESR1mutationswere found in theplasmaof 25.3%of patients (91of 360), ofwhom28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P , .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required. J Clin Oncol 34:2961-2968. © 2016 by American Society of Clinical Oncology
Methylenetetrahydrofolate reductase C677T polymorphism in Iraqi patients with ischemic stroke.

BACKGROUND
Data are conflicting concerning the association between ischemic stroke and methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Studies addressing this matter in developing countries are limited.


AIM
This study was undertaken to evaluate MTHFR C677T gene polymorphism as a possible risk factor in patients with ischemic stroke in Iraq.


SETTINGS AND DESIGN
A case-control study in a major teaching hospital in Northern Iraq.


MATERIALS AND METHODS
Study population included 70 patients with ischemic stroke diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI) and 50 controls matched by age and sex. All the patients and controls had detailed neurologic examination and blood sugar, lipid profile, total homocysteine, as well as, MTHFR gene analysis. The MTHFR C677T mutation status was detected in the amplified products using reverse hybridization to specific mutant and wild oligonucleotide probes by a colorimetric microwell plate method.


STATISTICAL ANALYSIS
Mann-Whitney U test and Chi-square tests were used to find the significance.


RESULTS
The median age of the patients was 60 years and 54% were males. The MTHFR C677T gene analysis detected TT genotype in 20% of patients and in 6% of controls and CC genotype in 37% of the patients and in 54% of the controls. The calculated risk of ischemic stroke in the subjects with TT genotype was 4.85 times more than the subjects with CC genotype (P = 0.03). Serum homocysteine level was significantly higher in the patients than the controls (P = 0.02). The serum homocysteine levels were significantly higher in those with TT and CT genotypes when compared to those with CC genotype (P < 0.001 and P = 0.04, respectively).


CONCLUSION
In the Iraq population studied MTHFR C677T TT genotype was a significant risk factor for ischemic stroke and it was related to the increased total homocysteine levels and the risk for ischemic stroke was graded with increasing MTHFR 677T allele dose.
Simultaneous densification and phase decomposition of TiB2-WB2 solid solutions activated by cobalt boride addition

Abstract In order to apply simultaneous densification and phase decomposition of TiB 2 –WB 2 solid solutions occurred by pressureless sintering using induction heating, the effect of CoB as the additive agent have been investigated. The sintered products were evaluated using X-ray diffraction, scanning electron microscopy and energy dispersive spectroscopy analyses. Dense product with a relative density of 95%, which was produced with a CoB addition of 0.5 wt.% and an induction heating time for 600 s, was identified as (Ti,W)B 2 and (W,Ti)B 2 phases. Platelet crystals of the (W,Ti)B 2 phase were precipitated in grain boundary of the (Ti,W)B 2 phase. The mechanical properties of the product, which improved by the densification and decomposition of (Ti,W)B 2 , are also presented.
The "MESACA" study: methylsulfonylmethane and boswellic acids in the treatment of gonarthrosis.

INTRODUCTION
Osteoarthritis is a chronic rheumatoid disease mediated by metalloproteinases and inflammatory cytokines. Methylsulfonylmethane (MSM) and boswellic acids (BA) each show promise in the treatment of inflammatory processes, but the efficacy of combined treatment with these substances in the treatment of arthritis has not yet been studied.


METHODS
In this prospective randomized clinical trial, MESACA (for "methylsulfonylmethane and boswellic acids in the treatment of knee arthritis"), 60 subjects affected by arthritis of the knee were randomly assigned to an experimental group treated for 60 days with 5 g of MSM and 7.2 mg of BA daily, or a control group which was administered a placebo. At 2 and 6 months follow-up (FU), the efficacy of combined treatment with these two dietary supplements was assessed using the visual analog pain scale (VAS) and the Lequesne index (LI) for joint function, as well as monitoring the use of anti-inflammatory drugs (nonsteroidal anti-inflammatory drugs and anti-cyclooxygenase-2).


RESULTS
Pain, assessed with the VAS scale, was worse in the group treated with MSM and BA as compared with the placebo group at 2 months FU (3.8 vs. 2.7; P=0.04), whereas no difference between the two groups was observed at 6 months FU (2.7 vs. 3.6; P=0.2). No statistically significant differences were found in the LI between the two groups at either FU (2 months: 4.8 vs. 4.2; P=0.51; 6 months: 4.4 vs. 4.5; P=0.91). By contrast, a statistically significant difference in patients need for anti-inflammatory drugs was seen in the experimental as compared to the placebo group, even by 2 months FU (0.2 vs. 0.6 tablets/day; P<0.0001), that persisted up to the end of the study (0.1 vs. 0.6 tablets/day; P<0.0001).


CONCLUSIONS
Although the combined administration of MSM and BA in the treatment of gonarthrosis was not shown to be more efficacious than placebo in the management of the clinical and functional picture, it significantly reduced patients need for anti-inflammatory drugs.
Investigation of the CasCor Family of Learning Algorithms

Six learning algorithms are investigated and compared empirically. All of them are based on variants of the candidate training idea of the Cascade Correlation method. The comparison was performed using 42 different datasets from the PROBEN1 benchmark collection. The results indicate: (1) for these problems it is slightly better not to cascade the hidden units; (2) error minimization candidate training is better than covariance maximization for regression problems but may be a little worse for classification problems; (3) for most learning tasks, considering validation set errors during the selection of the best candidate will not lead to improved networks, but for a few tasks it will. Copyright 1997 Elsevier Science Ltd.
Mobile-phone addiction in adolescence : The Test of Mobile Phone Dependence ( TMD )

__________________________________________________________________________________________ Introduction: The mobile phone is among the technological tools with the greatest presence in the market. During a period of scarcely 10 years, it has gone from being almost non-existent to being the device most used (and desired) by adolescents. Its physical characteristics as well as the psychological processes involved in its use explain both the fascination it elicits and the abuse or dependence it can come to provoke or encourage in adolescents. This study entailed the development and evaluation of a questionnaire designed to evaluate dependence on the mobile phone. Materials and methods: The items included in this instrument were developed based on criteria contained in the Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR; American Psychiatric Association, 2000) for dependence disorder. The questionnaires were administered to a total of 2,486 adolescents aged 12–18 years of age, and factor analyses were then performed. Results: The questionnaire is characterised by good psychometric properties as well as by the ability to discriminate between sexes and among age groups in an adolescent sample. The factors comprising this instrument are congruent with the concept of dependence as defined in the DSM-IV-TR. The process by which this questionnaire was developed is described, and the final version of the questionnaire is presented. Conclusion: The Test of Mobile Phone Dependence (TMP) is a questionnaire built taking into account the dependence criteria of DSM-IVTR. The process by which this questionnaire was developed is described, and the final version of the questionnaire is presented.
A novel approach for network on chip emulation

Current systems-on-chip execute applications that demand extensive parallel processing. Networks-on-chip (NoC) provide a structured way of realizing interconnections on silicon, and obviate the limitations of bus-based solutions. NoCs can have regular or ad hoc topologies, and functional validation is essential to assess their correctness and performance. In this paper, we present a flexible emulation environment implemented on an FPGA that is suitable to explore, evaluate and compare a wide range of NoC solutions with a very limited effort. Our experimental results show a speed-up of four orders of magnitude with respect to cycle-accurate HDL simulation, while retaining cycle accuracy. With our emulation framework, designers can explore and optimize a range of solutions, as well as characterize quickly performance figures.
A renaissance of neural networks in drug discovery.

INTRODUCTION
Neural networks are becoming a very popular method for solving machine learning and artificial intelligence problems. The variety of neural network types and their application to drug discovery requires expert knowledge to choose the most appropriate approach.


AREAS COVERED
In this review, the authors discuss traditional and newly emerging neural network approaches to drug discovery. Their focus is on backpropagation neural networks and their variants, self-organizing maps and associated methods, and a relatively new technique, deep learning. The most important technical issues are discussed including overfitting and its prevention through regularization, ensemble and multitask modeling, model interpretation, and estimation of applicability domain. Different aspects of using neural networks in drug discovery are considered: building structure-activity models with respect to various targets; predicting drug selectivity, toxicity profiles, ADMET and physicochemical properties; characteristics of drug-delivery systems and virtual screening.


EXPERT OPINION
Neural networks continue to grow in importance for drug discovery. Recent developments in deep learning suggests further improvements may be gained in the analysis of large chemical data sets. It's anticipated that neural networks will be more widely used in drug discovery in the future, and applied in non-traditional areas such as drug delivery systems, biologically compatible materials, and regenerative medicine.
A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis

OBJECTIVE
Etrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.


DESIGN
In the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).


RESULTS
In the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.


CONCLUSION
Etrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.
Statistical Models of Natural Images and Cortical Visual Representation

A fundamental question in visual neuroscience is: Why are the response properties of visual neurons as they are? A modern approach to this problem emphasizes the importance of adaptation to ecologically valid input, and it proceeds by modeling statistical regularities in ecologically valid visual input (natural images). A seminal model was linear sparse coding, which is equivalent to independent component analysis (ICA), and provided a very good description of the receptive fields of simple cells. Further models based on modeling residual dependencies of the ''independent" components have later been introduced. These models lead to emergence of further properties of visual neurons: the complex cell receptive fields, the spatial organization of the cells, and some surround suppression and Gestalt effects. So far, these models have concentrated on the response properties of neurons, but they hold great potential to model various forms of inference and learning.
Evolution of high-speed operational amplifier architectures

Strengths and weaknesses of modern widebandwidth bipolar transistor operational amplifiers are investigated and compared with respect to bandwidth, slew rate, noise, distortion, and power. This paper traces the evolution of operational amplifier designs since vacuum tube days to give a perspective of the large number of circuit variations used over time. Of particular value is the ability to use many of these circuit design options as the basis of new amplifiers. In addition, an array of operational amplifier components fabricated on the AT&T CBIC V2 [1] process is described. This design incorporates many of the architectural techniques that Vin have evolved over the years to produce four separate operational amplifier on a single base wafer. The process design methodology requires identifying the common elements in each architecture and the minimum number of additional components required to implement four unique architectures on the array. +V
The Prevalence of Inpatients at 33 U.S. Hospitals Appropriate for and Receiving Referral to Palliative Care.

BACKGROUND
The extent of unmet need for palliative care in U.S. hospitals remains largely unknown. We conducted a multisite cross-sectional, retrospective point prevalence analysis to determine the size and characteristics of the population of inpatients at 33 U.S. hospitals who were appropriate for palliative care referral, as well as the percentage of these patients who were referred for and/or received palliative care services. We also conducted a qualitative assessment of barriers and facilitators to referral, focusing on organizational characteristics that might influence palliative care referral practices.


METHODS
Patients appropriate for palliative care referral were defined as adult (≥18 years) patients with any diagnosis of a poor-prognosis cancer, New York Heart Association class IV congestive heart failure, or oxygen-dependent chronic obstructive pulmonary disease who had inpatient status in 1 of 33 hospitals on May 13, 2014. Qualitative assessment involved interviews of palliative care team members and nonpalliative care frontline providers.


RESULTS
Nearly 19% of inpatients on the point prevalence day were deemed appropriate for palliative care referral. Of these, approximately 39% received a palliative care referral or services. Delivery of palliative care services to these patients varied widely among participating hospitals, ranging from approximately 12% to more than 90%. Factors influencing differences in referral practices included nonstandardized perceptions of referral criteria and variation in palliative care service structures.


CONCLUSION
This study provides useful information to guide providers, administrators, researchers, and policy experts in planning for optimal provision of palliative care services to those in need.
SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-α Signaling

UNLABELLED
The transcription factor sex determining region (Y SRY)-box 2 (SOX2) is known to play a crucial role in the maintenance of self renewal or pluripotency of undifferentiated embryonic and neuronal stem cells. An elevated expression of SOX2 has been correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). We sought to investigate the mechanism(s) by which SOX2 modulates the ESCC metastasis. The SOX2 coding DNA sequence was inserted into pCMV vector and stably transfected in ESCC cells (Eca-109). The effect of SOX2 over expression was evaluated on cell migration, invasion and epithelial to mesenchymal transition (EMT). We also measured the expression of Slug to explore if this transcription factor is involved in SOX2-mediated regulation of cell migration/invasion and EMT. In addition, we determined the role of STAT3/HIF-1α to further probe the mechanism of SOX2-mediated metastasis via Slug. Our results demonstrated that SOX2 over expressing Eca-109 cells showed an enhanced cell migration/invasion. Moreover, these cells exhibited the EMT characteristics, that is, a significantly suppressed expression of the epithelial cells marker with a concomitant enhancement of those of the mesenchymal markers. An increased expression of Slug in SOX2 over expressing cells suggested the involvement of this transcription factor in SOX2-regulated metastasis. Whereas the expressions of STAT3/HIF-1α were found to be up-regulated in SOX2 expressing cells, blockade of these transcription factors resulted in the inhibition of Slug expression at both protein and mRNA levels.


CONCLUSION
These results suggest that SOX2 promoted the metastasis of ESCC, at least in part, by modulating Slug expression through the activation of STAT3/HIF-1α signaling.
Cost effective management programme for heart failure reduces hospitalisation.

OBJECTIVE
To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure.


DESIGN
Prospective, randomised trial.


SETTING
University hospital with a primary catchment area of 250,000 inhabitants.


PATIENTS
190 patients (aged 65-84 years, 52.3% men) hospitalised because of heart failure.


INTERVENTION
Two types of patient management were compared. The intervention group received education on heart failure and self management, with follow up at an easy access, nurse directed outpatient clinic for one year after discharge. The control group was managed according to routine clinical practice.


MAIN OUTCOME MEASURES
Time to readmission, days in hospital, and health care costs during one year.


RESULTS
The one year survival rate was 71.8% (n = 79) in the control group and 70.0% (n = 56) in the intervention group (NS). The mean time to readmission was longer in the intervention group than in the control group (141 (87) v 106 (101); p < 0.05) and number of days in hospital tended to be fewer (4.2 (7.8) v 8.2 (14.3); p = 0.07). There was a trend towards a mean annual reduction in health care costs per patient of US$1300 (US $1 = SEK 7.76) in the intervention group compared with costs in the controls (US$3594 v 2294; p = 0.07).


CONCLUSIONS
A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission.