Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized 19F MRS pharmacokinetic studies of 5‐fluorouracil

Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE‐MRI with the contrast agent Gd‐DTPA for tumor response to first‐line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5‐fluorouracil (FU) uptake, retention and catabolism as measured by localized 19F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between 19F MRS and the DCE‐MRI parameters kep, Ktrans and ve was also examined ( 1 ). In this study, 37 patients were included. The kinetic parameters of DCE‐MRI, kep, Ktrans and ve, before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first‐line treatment. No evident correlations between 19F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant Ktrans, as measured by DCE‐MRI before start of treatment, was negatively correlated with FU half‐life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor. Copyright © 2006 John Wiley & Sons, Ltd.
Performance Evaluation of LTE and Wi-Fi Coexistence in Unlicensed Bands

The deployment of modern mobile systems has faced severe challenges due to the current spectrum scarcity. The situation has been further worsened by the development of different wireless technologies and standards that can be used in the same frequency band. Furthermore, the usage of smaller cells (e.g. pico, femto and wireless LAN), coexistence among heterogeneous networks (including amongst different wireless technologies such as LTE and Wi-Fi deployed in the same frequency band) has been a big field of research in the academy and industry. In this paper, we provide a performance evaluation of coexistence between LTE and Wi-Fi systems and show some of the challenges faced by the different technologies. We focus on a simulator-based system- level analysis in order to assess the network performance in an office scenario. Simulation results show that LTE system performance is slightly affected by coexistence whereas Wi-Fi is significantly impacted by LTE transmissions. In coexistence, the Wi-Fi channel is most often blocked by LTE interference, making the Wi-Fi nodes to stay on the LISTEN mode more than 96% of the time. This reflects directly on the Wi-Fi user throughput, that decreases from 70% to ≈100% depending on the scenario. Finally, some of the main issues that limit the LTE/Wi-Fi coexistence and some pointers on the mutual interference management of both the systems are provided.
TCF: Lady Justice Casting the Final Verdict on the Outcome of Wnt Signalling

Abstract The Wnt signalling cascade plays an important role during embryonic patterning and cell fate determination and is highly conserved throughout evolution. Factors of the TCF/LEF HMG domain family (Tcfs) are the downstream effectors of this signal transduction pathway. Upon Wnt signalling, a cascade is initiated that results in the translocation of βcatenin to the nucleus, where it interacts with Tcf to generate a transcriptionally active complex. This bipartite transcription factor is targeted to the upstream regulatory regions of Tcf target genes. In the absence of Wnt signals, βcatenin is degraded in the cytoplasm via the ubiquitinproteasome pathway. Several proteins are instrumental in achieving this tight regulation of βcatenin levels in the cell, including adenomatous polyposis coli (APC), GSK3 β, and Axin/Conductin. Deregulation of the Wnt signalling pathway is implicated in several forms of cancer, such as colon carcinoma and melanoma. This deregulation is achieved via mutation of APC, βcatenin or Axin, resulting in elevated βcatenin levels and the presence of constitutively active Tcfβcatenin complexes in the nucleus. The accompanying inappropriate activation of target genes is considered to be a critical, early event in this carcinogenesis. In addition to regulating βcatenin levels, normal healthy cells have evolved a second level of regulation, by manipulating the activity of the Tcf proteins themselves. In the absence of Wnt signalling, Tcf complexes with several transcriptional repressor proteins ensuring active repression of Tcf target genes. In this review the dual role of Tcf proteins in the Wnt signalling cascade will be discussed.
Association of HLA‐DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort

Background and objective: The HLA‐DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA‐DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS.
Lagrangian Transport Through Surfaces in Volume-Preserving Flows

Advective transport of scalar quantities through surfaces is of fundamental importance in many scientific applications. From the Eulerian perspective of the surface it can be quantified by the well-known integral of the flux density. The recent development of highly accurate semi-Lagrangian methods for solving scalar conservation laws and of Lagrangian approaches to coherent structures in turbulent (geophysical) fluid flows necessitate a new approach to transport from the (Lagrangian) material perspective. We present a Lagrangian framework for calculating transport of conserved quantities through a given surface in $n$-dimensional, fully aperiodic, volume-preserving flows. Our approach does not involve any dynamical assumptions on the surface or its boundary.
Improving the torque output in radial- and axial-flux permanent-magnet synchronous machines with concentrated windings by using a combined wye-delta connection

In this paper, a combined wye-delta connection is introduced and compared with a common wye-connection of a concentrated winding. Because the combined wye-delta connection has a higher fundamental winding factor, the output torque is higher for the same current density when a sinusoidal current is imposed. As the combined wye-delta connection has only a minor influence on the losses in the machine, the efficiency of the machine is also increased. The combined wye-delta connection is illustrated in detail for an axial-flux permanent-magnet synchronous machine with a rated power of 4.5 kW at a fixed speed of 2500 rpm, using finite element computation.
Demonstration of a second rapidly conducting cortico‐diaphragmatic pathway in humans

Functional imaging studies in normal humans have shown that the supplementary motor area (SMA) and the primary motor cortex (PMC) are coactivated during various breathing tasks. It is not known whether a direct pathway from the SMA to the diaphragm exists, and if so what properties it has. Using transcranial magnetic stimulation (TMS) a site at the vertex, representing the diaphragm primary motor cortex, has been identified. TMS mapping revealed a second area 3 cm anterior to the vertex overlying the SMA, which had a rapidly conducting pathway to the diaphragm (mean latency 16.7 ± 2.4 ms). In comparison to the vertex, the anterior position was characterized by a higher diaphragm motor threshold, a greater proportional increase in motor‐evoked potential (MEP) amplitude with voluntary facilitation and a shorter silent period. Stimulus–response curves did not differ significantly between the vertex and anterior positions. Using paired TMS, we also compared intracortical inhibition/facilitation (ICI/ICF) curves. In comparison to the vertex, the MEP elicited from the anterior position was not inhibited at short interstimulus intervals (1–5 ms) and was more facilitated at long interstimulus intervals (9–20 ms). The patterns of response were identical for the costal and crural diaphragms. We conclude that the two coil positions represent discrete areas that are likely to be the PMC and SMA, with the latter wielding a more excitatory effect on the diaphragm.
Genetic diversity of symbiotic cyanobacteria in Cycas revoluta (Cycadaceae).

The diversity of cyanobacterial species within the coralloid roots of an individual and populations of Cycas revoluta was investigated based on 16S rRNA gene sequences. Sixty-six coralloid roots were collected from nine natural populations of cycads on Kyushu and the Ryukyu Islands, covering the entire distribution range of the species. Approximately 400 bp of the 5'-end of 16S rRNA genes was amplified, and each was identified by denaturing gradient gel electrophoresis. Most coralloid roots harbored only one cyanobiont, Nostoc, whereas some contained two or three, representing cyanobiont diversity within a single coralloid root isolated from a natural habitat. Genotypes of Nostoc within a natural population were occasionally highly diverged and lacked DNA sequence similarity, implying genetic divergence of Nostoc. On the other hand, Nostoc genotypes showed no phylogeographic structure across the distribution range, while host cycads exhibited distinct north-south differentiation. Cycads may exist in symbiosis with either single or multiple Nostoc strains in natural soil habitats.
The Utility of Capsule Endoscopy Small Bowel Surveillance in Patients with Polyposis

BACKGROUND:Small intestinal (SI) surveillance is recommended for polyposis patients. The utility and safety of capsule endoscopy (CE) for surveillance of SI neoplasia in patients with familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS) is unknown.METHODS:CE was offered to consecutive FAP and PJS patients due for routine upper endoscopic surveillance. The prevalence, location (jejunum, ileum), size (1–5 mm, 6–10 mm, >10 mm) and number (1–5, 6–12, >20) of polyps detected by CE was assessed.RESULTS:19 subjects (15 FAP/4 PJS) with a mean age of 43 were included. All subjects had previous intestinal surgery. No complications occurred with CE. CE in FAP: 9/15 (60%) of subjects with FAP had SI polyps. The prevalence of SI polyps was related to the duodenal polyposis stage and subject age. The location, size and number of polyps progressed as duodenal polyposis stage advanced. CE in PJS: 3/4 (75%) of subjects with PJS had SI polyps. The polyps were diffuse in 2/4 and only in the ileum in one subject. CE findings led to laparotomy with intra-operative endoscopic polypectomy in two PJS patients.CONCLUSION:SI polyps are common in FAP but their importance is unknown. CE should be performed in FAP patients with stage III and IV duodenal disease. Clinically significant polyps are commonly detected by CE in PJS and lead to change in management in 50% of PJS subjects. CE should replace radiographic SI surveillance for PJS patients. CE is safe in polyposis patients who have undergone major intestinal surgery.
The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis

SMAP2 is an Arf GAP and modulates clathrin-coated vesicle formation. SMAP2-deficient male mice exhibited globozoospermia due to acrosome deformation. In SMAP2(−/−) spermatids, budding of proacrosomal vesicles from the TGN was distorted and clathrin traffic–related molecules such as CALM and syntaxin2 were mislocated.
Methodological and Technical Issues for Integrating Functional Magnetic Resonance Imaging Data in a Neuronavigational System

OBJECTIVEThe aim of this article was to analyze the technical and methodological issues resulting from the use of functional magnetic resonance image (fMRI) data in a frameless stereotactic device for brain tumor or pain surgery (chronic motor cortex stimulation). METHODSA total of 32 candidates, 26 for brain tumor surgery and six chronic motor cortex stimulation, were studied by fMRI scanning (61 procedures) and intraoperative cortical brain mapping under general anesthesia. The fMRI data obtained were analyzed with the Statistical Parametric Mapping 99 software, with an initial analysis threshold corresponding to P < 0.001. Subsequently, the fMRI data were registered in a frameless stereotactic neuronavigational device and correlated to brain mapping. RESULTSCorrespondence between fMRI-activated areas and cortical mapping in primary motor areas was good in 28 patients (87%), although fMRI-activated areas were highly dependent on the choice of paradigms and analysis thresholds. Primary sensory- and secondary motor-activated areas were not correlated to cortical brain mapping. Functional mislocalization as a result of insufficient correction of the echo-planar distortion was identified in four patients (13%). Analysis thresholds (from P < 0.0001 to P < 10−12) more restrictive than the initial threshold (P < 0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data could be matched to cortical mapping spatial data. These analysis thresholds were not predictable preoperatively. Maximal tumor resection was accomplished in all patients with brain tumors. Chronic motor cortex electrode placement was successful in each patient (significant pain relief >50% on the visual analog pain scale). CONCLUSIONIn brain tumor surgery, fMRI data are helpful in surgical planning and guiding intraoperative brain mapping. The registration of fMRI data in anatomic slices or in the frameless stereotactic neuronavigational device, however, remained a potential source of functional mislocalization. Electrode placement for chronic motor cortex stimulation is a good indication to use fMRI data registered in a neuronavigational system and could replace somatosensory evoked potentials in detection of the central sulcus.
Predictors of treatment response to brief behavioral treatment of insomnia (BBTI) in older adults.

STUDY OBJECTIVES The extant literature on predictors of treatment response to behavioral treatments for insomnia is equivocal and limited in scope. The current study examined demographic, clinical, and sleep characteristics as predictors of clinically significant treatment response to brief behavioral treatment of insomnia (BBTI) in older adults with insomnia. METHODS Thirty-nine older adults with insomnia (67% females, mean age: 72.54 years) were randomized to BBTI treatment. Treatment outcomes were defined according to 2 criteria: (1) "response," defined as change in Pittsburgh Sleep Quality Index (PSQI) score ≥ 3 points or increase in sleep diary sleep efficiency ≥ 10%); or (2) remission, defined as absence of a clinical diagnosis of insomnia according to standard diagnostic criteria. Logistic regression examined whether baseline demographic, clinical, or sleep characteristics predicted treatment outcomes at 1 month follow-up. RESULTS Demographic variables did not predict treatment outcomes for either criterion. Higher anxiety, depression, poorer sleep quality, and longer polysomnography (PSG)-assessed sleep latency predicted greater likelihood of response at follow-up (p < 0.05). Longer sleep duration at baseline (measured by sleep diary and PSG) predicted greater likelihood of the remission at follow-up (p < 0.05). CONCLUSION Patients with insomnia who have greater distress at baseline or prolonged sleep latency are more likely to show positive response to BBTI. In contrast, short sleepers at baseline are less likely to have resolution of insomnia diagnosis following BBTI, perhaps due to the sleep restriction component of the treatment. Identifying the characteristics that predict positive BBTI treatment outcomes can facilitate personalized behavioral treatments to improve outcomes.
ASSOCIATION OF INTERLEUKIN-10 PROMOTER POLYMORPHISM WITH THE INCIDENCE OF MULTIPLE ORGAN DYSFUNCTION FOLLOWING MAJOR TRAUMA: RESULTS OF A PROSPECTIVE PILOT STUDY

A dysbalanced immune response is thought to account for a substantial part of the morbidity and mortality after severe trauma. The cytokine interleukin-10 (IL-10) suppresses the transcription of proinflammatory cytokines, mainly in macrophages and monocytes. The objectives of this prospective study in a level I trauma center in Germany were to examine the distribution of IL-10 promoter polymorphisms in a cohort of severely injured patients, to measure IL-10 cytokine levels and relate these to the genotype, and to identify associations of IL-10 polymorphisms with the incidence of severe multiple organ dysfunction syndrome (MODS). The genotypes of polymorphisms −592 and −1082 were determined by polymerase chain reaction (PCR) and restriction cleavage with Rsa 1 or Mnl I, respectively. We analyzed 119 severely injured trauma patients [mean Injury Severity Score (ISS) 38.0 ± 13.2]. The frequency of the −1082A allele was 0.542, and that of the −592C allele was 0.807. IL-10 polymorphisms were not significantly associated with mean systemic IL-10 cytokine levels 6, 12, and 18 h after admission to the ICU. Carriers of the genotype −592AC had significantly higher overall MOD scores than non-AC carriers (P = 0.018; Pcorr = 0.036). The genotypes of the IL-10 SNP −1082 were not significantly associated with MOD scores. A multivariate Cox hazard regression analysis including important factors of the patients’ anatomic and physiological trauma impact revealed only the shock index, the severity of the head injury, and the IL-10 −592 genotype AC as significant independent risk factors for the development of MODS. In this multivariate analysis, carriers of the genotype −592AC displayed a 3.3-fold increase in the relative risk of developing a MODS (P = 0.008, hazard ratio 3.29, 95% CI 1.36–7.97). Our data suggest a possible link between the AC genotype of the −592 single nucleotide polymorphism and significantly higher mean MOD scores. The AC genotype was associated in multivariate analysis with a higher relative risk of MODS in multiply injured patients. Further investigations in larger cohorts need to focus on the potential diagnostic and therapeutic options of this SNP.
Bacterial Siderophores Hijack Neutrophil Functions

Neutrophils are the primary immune cells that respond to inflammation and combat microbial transgression. To thrive, the bacteria residing in their mammalian host have to withstand the antibactericidal responses of neutrophils. We report that enterobactin (Ent), a catecholate siderophore expressed by Escherichia coli, inhibited PMA-induced generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in mouse and human neutrophils. Ent also impaired the degranulation of primary granules and inhibited phagocytosis and bactericidal activity of neutrophils, without affecting their migration and chemotaxis. Molecular analysis revealed that Ent can chelate intracellular labile iron that is required for neutrophil oxidative responses. Other siderophores (pyoverdine, ferrichrome, deferoxamine) likewise inhibited ROS and NETs in neutrophils, thus indicating that the chelation of iron may largely explain their inhibitory effects. To counter iron theft by Ent, neutrophils rely on the siderophore-binding protein lipocalin 2 (Lcn2) in a “tug-of-war” for iron. The inhibition of neutrophil ROS and NETs by Ent was augmented in Lcn2-deficient neutrophils compared with wild-type neutrophils but was rescued by the exogenous addition of recombinant Lcn2. Taken together, our findings illustrate the novel concept that microbial siderophore’s iron-scavenging property may serve as an antiradical defense system that neutralizes the immune functions of neutrophils.
An Overview of the North American Residential Radon and Lung Cancer Case-Control Studies

Lung cancer has held the distinction as the most common cancer type worldwide since 1985 (Parkin et al., 1993). Recent estimates suggest that lung cancer accounted for 1.2 million deaths worldwide in 2002, which represents 17.6% of the global cancer deaths (Parkin et al., 2005). During 2002, the highest lung cancer rates for men worldwide reportedly occurred in North America and Eastern Europe, whereas the highest rates in females occurred in North America and Northern Europe (Parkin et al., 2005). While tobacco smoking is the leading risk factor for lung cancer, because of the magnitude of lung cancer mortality, even secondary causes of lung cancer present a major public health concern (Field, 2001). Extrapolations from epidemiologic studies of radon-exposed miners project that approximately 18,600 lung cancer deaths per year (range 3000 to 41,000) in the United States alone are attributable to residential radon progeny exposure (National Research Council, 1999). Because of differences between the mines and the home environment, as well as differences (such as breathing rates) between miners and the general public, there was a need to directly evaluate effects of radon in homes. Seven major residential case-control radon studies have been conducted in North America to directly examine the association between prolonged radon progeny (radon) exposure and lung cancer. Six of the studies were performed in the United States including studies in New Jersey, Missouri (two studies), Iowa, and the combined states study (Connecticut, Utah, and southern Idaho). The seventh study was performed in Winnipeg, Manitoba, Canada. The residential case-control studies performed in the United States were previously reviewed elsewhere (Field, 2001). The goal of this review is to provide additional details regarding the methodologies and findings for the individual studies. Radon concentration units presented in this review adhere to the types (pCi/L or Bq/m3) presented in the individual studies. One picocurie per liter is equivalent to 37 Bq/m3. Because the Iowa study calculated actual measures of exposure (concentration × time), its exposures estimates are presented in the form WLM5–19 (Field et al., 2000a). WLM5–19 represents the working level months for exposures that occurred 5–19 yr prior to diagnosis for cases or time of interview for control. Eleven WLM5–19 is approximately equivalent to an average residential radon exposure of 4 pCi/L for 15 yr, assuming a 70% home occupancy. Ernest G. Létourneau and Janet B. Schoenberg are retired; Jan A. Stolwijk has emeritus status. Salary support for Drs. Steck and Field was provided in part by grant numbers R01 ES05653 and P30 ES05605 from the National Institute of Environmental Health Sciences, NIH and grant number R01 CA85942 from the National Cancer Institute, NIH.