Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomized phase II study of pemetrexed versus pemetrexed plus erlotinib in second-line treatment for locally advanced or metastatic, nonsquamous NSCLC.

7526 Background: PEM and ERL have been approved as second-line monotherapy for locally advanced or metastatic NSCLC. The combination of PEM + ERL showed synergistic activity in preclinical studies. This multicenter, randomized, open-label study assessed the efficacy and safety of PEM + ERL vs PEM. METHODS Patients (pts) with NSQ NSCLC who have failed one prior platinum-based chemotherapy regimen for advanced or metastatic disease, ≥1 measurable lesion by RECIST, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 were eligible. Pts received PEM 500 mg/m2 (with vitamin B12 and folic acid supplementation) q3w alone or combined with ERL 150 mg daily until progression. The primary endpoint of progression-free survival (PFS) was analyzed using the log-rank test with one-sided alpha of 0.20. RESULTS Of 165 pts with NSQ NSCLC who were randomized (PEM: 86; PEM + ERL: 79), 159 were treated (PEM: 83 and PEM + ERL: 76). The baseline characteristics for PEM/PEM + ERL were: median age of 61/64 yrs, stage IV disease in 84.3%/84.2%, and ECOG PS 2 in 13.3%/12.0% of pts. The median PFS (months) was 2.9 [95% CI: 1.9, 3.4] in PEM versus 3.2 [95% CI: 2.9, 4.7] in PEM + ERL (hazard ratio [HR] 0.63; 95% CI: 0.44, 0.90; log-rank P=0.005). The median overall survival (OS; months) was 7.8 [95% CI: 5.3, 10.4] in PEM versus 11.8 [95% CI: 8.2, 16.7] in PEM + ERL (HR 0.68; 95% CI: 0.47, 0.98; log-rank P=0.019). Response rates were 10.8% in PEM and 17.1% in PEM + ERL; disease-control rates were 51.8% in PEM and 55.3% in PEM + ERL. Two pts died in PEM + ERL due to drug-related lung abscess and febrile neutropenia. Study drug-related grade (G) 3 + 4 laboratory toxicities (in ≥10% of pts) in PEM/PEM + ERL were anemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%). G 3 + 4 non-laboratory drug-related toxicities (in ≥5% of pts) in PEM/PEM + ERL were rash (1.2%/9.2%), diarrhea (1.2%/5.3%), and febrile neutropenia (2.4%/10.5%). CONCLUSIONS PEM + ERL significantly improved PFS and OS compared with PEM, and was well tolerated. The benefit of this combination therapy should be confirmed in a phase III study.
The Effects of Methylglyoxal on Glutathione S-Transferase from Nicotiana tabacum

Methylglyoxal (MG) is one of the aldehydes that accumulate in plants under environmental stress. Glutathione S-transferases (GSTs) play important roles, including detoxification, in the stress tolerance systems of plants. To determine the effects of MG, we characterized recombinant GST. MG decreased GST activity and thiol contents with increasing K m. GST can serve as a target of MG modification, which is suppressed by application of reduced glutathione.
Impact of Protists on the Activity and Structure of the Bacterial Community in a Rice Field Soil

ABSTRACT Flooded rice fields have become a model system for the study of soil microbial ecology. In Italian rice fields, in particular, aspects from biogeochemistry to molecular ecology have been studied, but the impact of protistan grazing on the structure and function of the prokaryotic community has not been examined yet. We compared an untreated control soil with a γ-radiation-sterilized soil that had been reinoculated with a natural bacterial assemblage. In order to verify that the observed effects were due to protistan grazing and did not result from sterilization, we set up a third set of microcosms containing sterilized soil that had been reinoculated with natural assemblage bacteria plus protists. The spatial and temporal changes in the protistan and prokaryotic communities were examined by denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism (T-RFLP) analysis, respectively, both based on the small-subunit gene. Sequences retrieved from DGGE bands were preferentially affiliated with Cercozoa and other bacteriovorous flagellates. Without protists, the level of total DNA increased with incubation time, indicating that the level of the microbial biomass was elevated. Betaproteobacteria were preferentially preyed upon, while low-G+C-content gram-positive bacteria became more dominant under grazing pressure. The bacterial diversity detectable by T-RFLP analysis was greater in the presence of protists. The level of extractable NH4+ was lower and the level of extractable SO42− was higher without protists, indicating that nitrogen mineralization and SO42− reduction were stimulated by protists. Most of these effects were more obvious in the partially oxic surface layer (0 to 3 mm), but they could also be detected in the anoxic subsurface layer (10 to 13 mm). Our observations fit well into the overall framework developed for protistan grazing, but with some modifications pertinent to the wetland situation: O2 was a major control, and O2 availability may have limited directly and indirectly the development of protists. Although detectable in the lower anoxic layer, grazing effects were much more obvious in the partially oxic surface layer.
Smart antennas for mobile satellite communications

Smart antenna is important for satellite communications because it can increase the channel capacity, spectrum efficiency and coverage range of the communication systems. The smart antennas can be categorized into two types: beam-switching smart antenna and adaptive smart antenna. This paper overviews the technology for both types of smart arrays with general system architecture and design examples. A detailed list of references is given in the end of this paper.
Social Network Management Enhances Customer Relationship

The study aims to develop a framework of social network management to enhance customer relationship. Social network management of this research is derived from social network site management, individual and organization social network usage motivation. The survey was conducted with organization employees who have used social network to interact with customers. The results reveal that content, link, privacy and security, page design and interactivity are the major issues of social network site management. Content, link, privacy and security, individual and organization motivation have major impacts on encouraging business knowledge sharing among employees. Moreover, Page design and interactivity, content, organization motivation and knowledge sharing can improve customer relationships. Keywords—Social network management, social network site, motivation, knowledge sharing, customer relationship
Fractional Dynamics in Bioscience and Biomedicine and the Physics of Cancer

Almost all phenomena and structures in nature exhibit some degrees of fractionality or fractality. Fractional calculus and fractal theory are two interrelated concepts. In this article we study the memory effects in nature and particularly in biological structures. Based on this fact that natural way to incorporate memory effects in the modeling of various phenomena and dealing with complexities is using of fractional calculus, in this article we present different examples in various branch of science from cosmology to biology and we investigate this idea that are we able to describe all of such these phenomena using the well-know and powerful tool of fractional calculus. In particular we focus on fractional calculus approach as an effective tool for better understanding of physics of living systems and organism and especially physics of cancer.
The slow potentials of thoracic respiratory motoneurones and their relation to breathing

The alternating contractions of inspiratory and expiratory muscles causing the movements of breathing result from the alternating, periodic, repetitive discharge of inspiratory and expiratory motoneurones. In fact, however, nothing is known of the immediate cause of these activities although much has been learnt about the supra-spinal mechanisms which influence them. The need is thus indicated for a study of the mechanism of respiratory motoneurone discharge and to this end the technique of intracellular recording from neurones in the central nervous system (Brock, Coombs & Eccles, 1952; Woodbury & Patton, 1952) lends itself admirably. The present paper describes intracellular recordings from inspiratory and expiratory motoneurones of the thoracic spinal cord of spontaneously breathing, anaesthetized cats. A brief report of some of these results has been previously published (Eccles, Sears & Shealy, 1962). Intracellular recording from phrenic motoneurones under conditions of artificial respiration and in response to electrical stimulation within the medulla has recently been described by Gill & Kuno (1963).
Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity

Prokaryotic toxin–antitoxin (TA) loci consist of two genes in an operon that encodes a metabolically stable toxin and an unstable antitoxin. The antitoxin neutralizes its cognate toxin by forming a tight complex with it. In all cases known, the antitoxin autoregulates TA operon transcription by binding to one or more operators in the promoter region while the toxin functions as a co‐repressor of transcription. Interestingly, the toxin can also stimulate TA operon transcription. Here we analyse mechanistic aspects of how RelE of Escherichia coli can function both as a co‐repressor and as a derepressor of relBE transcription. When RelB was in excess to RelE, two trimeric RelB2•RelE complexes bound cooperatively to two adjacent operator sites in the relBE promoter region and repressed transcription. In contrast, RelE in excess stimulated relBE transcription and released the RelB2•RelE complex from operator DNA. A mutational analysis of the operator sites showed that RelE in excess counteracted cooperative binding of the RelB2•RelE complexes to the operator sites. Thus, RelE controls relBE transcription by conditional cooperativity.
Novel Methods in Nanomedicine for Drug Delivery Systems: Cancer Therapies

The recognition of new drug candidates for the remedy of illnesses such as cancer, infectious illnesses, allocates novel tasks for pharmaceutical technology [1]. With attention to drug delivery several problems happen like low bioavailability and hence low solubility or limitation to inappropriate paths of management. Nanotechnological near allow to circumvent several of these difficulties, therefore being well appropriate for future applications as nanomedicines. Furthermore, impressive and enough loading is an acute subject that is approached via nonspherical particles and/or via mesoporous particles both offering larger capacities and levels [2]. Particular attention is placed on the efficacy of figure of particulate materials on the body and associated physiological mechanisms [3]. The changed reply of biological systems on dissimilar shapes opens a novel dimension to regulate particle system interaction [4]. Eventually, the biological reply to these systems wills definition the destiny with respect to their therapeutic value. Consequently, the contact template among nonspherical particulate materials and biological systems as well as the manufacture developments are distinguished [5]. Nevertheless, significant development has been prepared so far during the progress of non spherical drug delivery systems. Also understanding and utilizing the modulation of biological replies by changing particulate figure, the growth of bioavailability of new drugs is a key, challenging difficult in modern drug delivery [6]. A resolution can be given by the use of nanoparticulate materials. While the potential of silica particles, e.g., for example gene carriers, has been shown widespread, the lately developed mesoporous silica nanoparticles permit the delivery of drug mixtures with poor solubility or the controlled deliverance of a drug over a longer time cycle [7]. Moreover, with respect to the use of more efficient and suitable paths of management these progresses will contribute to a more effective therapy in the future. This contains efforts to minimize therapeutic toxicity attended by a higher patient compliance and reduced health care prices. So, nanomedicine based on new methods for drug delivery systems is expected to develop a well-recognized term in modern medicine [8].
Giant Vacuole Survival Time and Implications for Aqueous Humor Outflow

PurposeA quantitative study was conducted to estimate the survival time of giant vacuoles of the endothelial wall of Schlemm's canal once perfusion pressure has dropped to zero. Vacuoles are known to be sensitive to intraocular pressure and could serve as real-time markers of aqueous pressure in the juxtacanalicular tissue if their survival time is short once pressure is lowered. MethodsSix pairs of healthy human eyes were perfused with phosphate-buffered saline. One eye was then fixed by perfusion, whereas the fellow eye was dissected into wedges and fixed by immersion at intervals ranging from 3 to 120 minutes after perfusion had been stopped. Light microscopy was used to determine the number of giant vacuoles on the inner and outer walls of Schlemm's canal. ResultsA 70% decrease in giant vacuole counts was found 3 minutes after discontinuation of saline perfusion when compared with perfusion-fixed fellow eyes (5.9 ± 4.0 vacuoles per histologic section versus 19.1 ± 9.0;P = 0.02). Vacuole counts continued to decrease with time so that by 120 minutes at zero pressure, vacuole counts were 12% of those in the perfusion-fixed eyes (88% decrease;P = 0.003). Giant vacuoles occurred on the inner and outer walls of the canal, but were more numerous on the inner wall. ConclusionsMost giant vacuoles have a short survival time, less than 3 minutes, once perfusion pressure decreases to zero. This suggests that they can respond rapidly to intraocular pressure changes and thus can serve as markers of aqueous pressure differences across the inner and outer walls of Schlemm's canal.
Knowledge of perfusion and contractile reserve improves the predictive value of recovery of regional myocardial function postrevascularization: a study using the combination of myocardial contrast echocardiography and dobutamine echocardiography.

BACKGROUND This study was designed to determine the value of myocardial contrast echocardiography (MCE) and dobutamine echocardiography (DE), alone or in combination, in predicting functional recovery in patients with resting wall motion abnormalities due to CAD. MCE and DE have been independently shown to be useful in detecting myocardial viability in the post-myocardial infarction setting. METHODS AND RESULTS Thirty-nine patients with significant coronary artery disease and resting wall motion abnormalities underwent DE (2.5 to 20 microg x kg(-1) x min(-1)) and wall motion analysis (16-segment model). MCE was performed with selective intracoronary injections of sonicated meglumine (2 cm3). Myocardial viability was defined as presence of contrast effect by MCE and contractile reserve or an ischemic response by DE. Functional recovery (improvement in wall motion) was assessed after revascularization (percutaneous transluminal coronary angioplasty, n=20; coronary artery bypass surgery, n=19). When the two groups of patients were analyzed, MCE was associated with excellent sensitivities (84%) yet poor specificities (19% to 26%); DE had lower sensitivities (79% to 80%) but also poor specificities (30% to 36%). The combination of both was associated with excellent sensitivities (90% to 93%) and modest specificities (48% to 50%) for predicting functional recovery. A biphasic response with DE was infrequent (14% to 42%) but highly specific of functional recovery (84% to 94%). MCE had an excellent negative predictive value for functional recovery (83%). CONCLUSIONS The prediction of functional recovery post-revascularization can be enhanced by combining MCE and DE.
Retrograde tracing of the subset of afferent connections in mouse barrel cortex provided by zincergic neurons

The barrel cortex of rodents is densely innervated by a prominent subclass of glutamatergic neurons that sequester and release zinc from their synaptic boutons. These neurons may play an important role in barrel cortex function and plasticity, as zinc has been shown to modulate synaptic function by regulating neurotransmitter release, excitatory and inhibitory amino acid receptors, and second messenger signaling cascades. Here, we utilized intracortical infusions of sodium selenite to identify the source of the zincergic innervation to the mouse barrel cortex. Our results demonstrate that the majority of zincergic projections to the barrel cortex arose from ipsilateral and callosal neurons, situated in cortical layers 2/3 and 6. Regionally, these labeled neurons were most abundant within the barrel cortex itself, posterior parietal association cortex, secondary somatosensory cortex, and motor cortex. Labeled neurons were also found in other somatosensory regions corresponding to the trunk, fore‐ and hindlimb, as well as more distant regions such as the visual, rhinal, dorsal peduncular and insular cortices, the claustrum, and lateral and basolateral amygdaloid nuclei. Further, some mice were injected with the retrograde tracer cholera toxin subunit B to compare retrograde labeling of zincergic neurons with that of the general population of neurons innervating the barrel cortex. Our data indicate that all cortical regions providing inputs to the barrel cortex possess a zincergic component, whereas those from thalamic or brainstem structures do not. These findings demonstrate that zincergic pathways comprise a chemospecific associational network that reciprocally interconnects the barrel cortex with other cortical and limbic structures. J. Comp. Neurol. 486:48–60, 2005. © 2005 Wiley‐Liss, Inc.
An Anycast Prefix for 6to4 Relay Routers

This memo introduces a "6to4 anycast address" in order to simplify the configuration of 6to4 routers. It also defines how this address will be used by 6to4 relay routers, how the corresponding "6to4 anycast prefix" will be advertised in the IGP and in the EGP. The memo documents the reservation by IANA (Internet Assigned Numbers Authority) of the "6to4 relay anycast prefix. "
Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family‐cancer database

The genetic and environmental components in 15 common cancers were estimated using the nationwide Swedish Family‐Cancer Database. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modeling was used to derive estimates of the importance of genetic and environmental effects. Statistically significant estimates of proportion of cancer susceptibility, accounted for by genetic effects, were obtained for all studied cancers except for leukemia. The estimate was highest in thyroid cancer (53%), followed by tumors at endocrine glands (28%), testis (25%), breast (25%), cervix (22%), melanoma (21%), colon (13%), nervous system (12%), rectum (12%), non‐Hodgkin lymphoma (10%), lung (8%), kidney (8%), urinary bladder (7%), stomach (1%) and leukemia (1%). The estimates of shared environmental effects ranged from 0% (cervix) to 15% (stomach). The childhood shared environmental effects were most important in testicular cancer (17%), stomach cancer (13%) and cervix in situ (13%). Our results indicate that environment has a principal causative role in cancer at all studied sites except for thyroid. The relatively large effect of heritability in cancer at some sites, on the other hand, indicates that even though susceptibility genes have been described at many cancer sites, they are likely to explain only part of the genetic effects. © 2002 Wiley‐Liss, Inc.
Experiência de fluxo na prática e aprendizagem musical

A Teoria do Fluxo de Csikszentmihalyi (2003, 1999, 1996, 1992, 1990) pode ser considerada como referencial significativo para os estudos sobre motivacao e pratica musical. De acordo com este autor, o envolvimento do sujeito de forma intensa numa determinada atividade pode gerar a experiencia de fluxo, caracterizada como um momento de imersao total numa atividade compativel com as habilidades do sujeito que leva uma excelente sensacao de bem estar, a ponto de alterar a percepcao do tempo. Este processo, se constante, favorece a aquisicao da personalidade autotelica, perfil caracterizado pelo aumento da capacidade de concentracao auto-estima e satisfacao. A teoria do fluxo tem sido utilizada em pesquisas sobre cognicao, aprendizagem e performance musical e muitos resultados significativos estao sendo apontados.
Increased risk of hepatocellular carcinoma in patients infected with hepatitis C genotype 1b.

UNLABELLED Infection with hepatitis C virus (HCV) genotype 1b has been reported to be associated with more severe liver disease and an unfavorable outcome. Liver transplantation allows for a complete examination of the explanted liver for the detection of hepatocellular carcinoma (HCC). OBJECTIVE To study the prevalence of HCC in patients with liver cirrhosis secondary to chronic infection with HCV genotype 1b compared with those infected with other genotypes. METHODS Sera were collected from 48 consecutive patients undergoing liver transplantation for end stage liver disease secondary to HCV infection. RNA was extracted from serum using chaotropic lysis and isopropanol precipitation. Reverse transcriptase-polymerase chain reaction of the NS5 region was performed, followed by automated sequencing on desalted amplification products. Genotype assignment followed Simmonds's classification. All explanted livers were examined for the presence of HCC. RESULTS HCV genotypes in our patients were as follows: subtype 1a, 20 patients (42%); 1b, 18 patients (37.5%); 2a, one patient (2%); 2b, six patients (12.5%); 3a, one patient (2%); and 4a, two patients (4%). Although five of 18 patients infected with HCV genotype 1b (28%) had HCC, only one of 30 patients (3%) infected with all other genotypes (1a, 2a, 2b, 3a, and 4a) had HCC (p = 0.02). CONCLUSION Infection with HCV genotype 1b may carry a higher risk for the development of HCC than infection with other HCV genotypes.
Gastrointestinal dysmotility: evidence and clinical management

Purpose of reviewGastrointestinal dysmotility and dysfunction underlie our difficulties in providing adequate nutrition by the enteral route to our critically ill patients. Recent findingsRecent studies have quantified gastric emptying and nutrient absorption. Slow gastric emptying is common and probably mediated by cholecystokinin and reduced active ghrelin concentrations. The cause of impaired nutrient absorption is not yet fully understood but may be related to small intestinal blood flow and/or mucosal factors. The absorption of the different macronutrients may be affected in different ways both by critical illness and by therapies. A better understanding of this may optimize the design of nutrient formulations in the future. New treatment modalities for gastrointestinal dysfunction are being investigated and include small intestinal feeding, nonpharmacological options such as acupuncture, and drugs including novel motilin receptor agonists, and opioid antagonists. SummaryWe are gradually developing a better understanding of how the gut works during critical illness, which has implications for optimizing the delivery of nutrition and thereby improving nutritional and clinical outcomes.