Miracle-dz/UniFAR-FTUs huggingface dataset:
The Qualification of Docetaxel or Erlotinib for Second-Line Therapy Should Be Based on Clinical and Molecular Predictive Factors

Background: We evaluated the effectiveness of docetaxel or erlotinib in second-line treatment of non-small cell lung cancer (NSCLC) and focused on the impact of predictive factors on the outcome of therapy. Methods: 204 patients with progressive disease after platinum-based therapy were enrolled: 102 received an infusion of 75 mg/m2 of docetaxel and 102 received 150 mg of erlotinib orally. Results: Response rate (RR) was 6.9 and 8.8% for docetaxel and erlotinib, respectively. Progression-free survival (PFS) was 1.2 months for docetaxel and 1.6 months for erlotinib (hazard ratio, HR = 1.2, p = 0.17). Overall survival was 5.5 versus 7 months for docetaxel and erlotinib, respectively (HR = 1.35, p = 0.06). Using Cox regression, we found clinical factors (performance status and weight loss) with predictive values for RR and PFS in second-line-treated patients. Prior radiotherapy, smoking status and EGFR mutation might help to predict outcome of erlotinib treatment and βIII-tubulin mRNA expression that of docetaxel, but histopathological diagnosis did not have any predictive value. Conclusions: Erlotinib and docetaxel show similar efficacy in the treatment of NSCLC. The application of predictive factors may facilitate qualification for second-line treatment with both drugs.
Transcriptomic and histopathological analysis of cholangiolocellular differentiation trait in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse aetiologies, morphologies and clinical outcomes. Recently, histopathological distinction of cholangiolocellular differentiation (CD) of iCCA has been suggested. However, its genome‐wide molecular features and clinical significance remain unclear.
Translucency and color match with a shade guide of esthetic brackets with the aid of a spectroradiometer

ABSTRACT Objective: Since the color of esthetic brackets should match that of teeth, the aims of this study were to determine the color and translucency of esthetic brackets by means of the clinically relevant use of a spectroradiometer, and to compare the color of brackets with that of a commercial shade guide. Methods: The color of central and tie-wing regions of four plastic and four ceramic brackets was measured according to the CIE L*a*b* color scale over white and black backgrounds. Brackets were classified into five groups based on their composition. The color of Vitapan Classical Shade Guide tabs was also measured. Translucency parameter (TP) and contrast ratio (CR) were calculated to determine translucency. Results: Color differences between brackets and the shade guide tabs were 10.4 - 34.5 ∆E*ab units. TP and CR values for the central region were 16.4 - 27.7 and 0.38 - 0.58, whereas for the tie-wings they were 24.0 - 39.9 and 0.25 - 0.45, respectively. The color coordinates, TP and CR values were significantly influenced by bracket composition and brand (p < 0.05). Conclusions: Esthetic brackets investigated herein showed unacceptable color differences (∆E*ab > 5.5) compared with the shade guide tabs. Differences in the translucency of brackets by brand were within the visually perceptible range (∆CR > 0.07). Therefore, brackets showing the best matching performance for each case should be selected considering esthetic and functional demands.
Biochemical Characterization of the Serum Fetuin-Mineral Complex*

The present study was carried out to characterize the fetuin-mineral complex (FMC), a high molecular mass complex of calcium phosphate mineral and the proteins fetuin and matrix Gla protein (MGP) that was initially discovered in serum of rats treated with etidronate and appears to play a critical role in inhibiting calcification in vivo. Fetuin purified from the FMC contains 3.3 mol of protein-bound phosphate. There is 1.3 mg of FMC/ml of serum 6 h after etidronate injection, and the FMC is 46% fetuin and 53% mineral by mass. Formation of the FMC in the first 6 h after etidronate injection does not increase serum fetuin despite the fact that 50% of serum fetuin is associated with the FMC, and clearance of the FMC in the 9–24-h interval lowers total serum fetuin by 50%. These observations suggest that the fetuin component of the FMC is derived from fetuin initially in serum and that clearance of the FMC removes the associated fetuin from circulation. One additional protein was consistently present in all preparations of the FMC, spp24 (secreted phosphoprotein 24). This 24-kDa protein is similar in domain structure to fetuin and, like fetuin and MGP, contains several residues of phosphoserine and accumulates in bone. Exogenous spp24 associated strongly with the FMC when added to serum containing it. These observations suggest that spp24 may, like fetuin and MGP, play a role in inhibiting calcification.
Electroacupuncture Analgesia Is Improved by Adenoviral Gene Transfer of Dopamine Beta-hydroxylase into the Hypothalamus of Rats

Electroacupuncture (EA) is a modified form of acupuncture that utilizes electrical stimulation. We previously showed that EA stimulated rats were divided into responders that were sensitive to EA and non-responders that were insensitive to EA based on the tail flick latency (TFL) test. The dopamine beta-hydroxylase (DBH) gene was more abundantly expressed in the hypothalamus of responder rats than non-responder rats. To determine whether overexpression of DBH gene expression in the hypothalamus modulate EA analgesia, we constructed a DBH encoding adenovirus and which was then injected into the hypothalamus of SD rats. Microinjection of DBH or control GFP virus into the hypothalamus had no changes on the basal pain threshold measured by a TFL test without EA treatment. However, the analgesic effect of EA was significantly enhanced from seven days after microinjection of the DBH virus, but not after injection of the control GFP virus. DBH expression was significantly higher in the hypothalamus of DBH virus injected rat than control GFP virus or PBS injected rats. Moreover, expression of the DBH gene did not affect the body core temperature, body weight, motor function or learning and memory ability. Although the functional role of DBH in the hypothalamus in the analgesic effect of EA remains unclear, our findings suggest that expression of the DBH gene in the hypothalamus promotes EA analgesia without obvious side-effects.
Olfaction, Emotion & the Amygdala: arousal-dependent modulation of long-term autobiographical memory and its association with olfaction: beginning to unravel the Proust phenomenon?

The sense of smell is set apart from other sensory modalities. Odours possess the capacity to trigger immediately strong emotional memories. Moreover, odorous stimuli provide a higher degree of memory retention than other sensory stimuli. Odour perception, even in its most elemental form olfaction already involves limbic structures. This early involvement is not paralleled in other sensory modalities. Bearing in mind the considerable connectivity with limbic structures, and the fact that an activation of the amygdala is capable of instantaneously evoking emotions and facilitating the encoding of memories, it is unsurprising that the sense of smell has its characteristic nature. The aim of this review is to analyse current understanding of higher olfactory information processing as it relates to the ability of odours to spontaneously cue highly vivid, affectively toned, and often very old autobiographical memories (episodes known anecdotally as Proust phenomena). Particular emphasis is placed on the diversity of functions attributed to the amygdala. It’s role in modulating the encoding and retrieval of long-term memory is investigated with reference to lesion, electrophysiological, immediate early gene, and functional imaging studies in both rodents and humans. Additionally, the influence of hormonal modulation and the adrenergic system on emotional memory storage is outlined. I finish by proposing a schematic of some of the critical neural pathways that underlie the odour-associated encoding and retrieval of emotionally toned autobiographical memories.
Recent Stem Cell Advances: Induced Pluripotent Stem Cells for Disease Modeling and Stem Cell–Based Regeneration

Currently, the only available cure for patients with end-stage heart failure is cardiac transplantation. A number of strategies to regenerate heart tissue have been devised to resolve the shortage of available transplantation organs, including transplantation of cardiomyocytes or cardiomyogenic stem cells. Stem cell research is actively pursuing strategies to yield new cell sources for use in regenerative medicine. Stem cells are classified into 2 types of cells, somatic stem cells and pluripotent stem cells. Somatic stem cells reside in various organs such as bone marrow, brain, liver, skeletal muscle, and dermal tissue. Somatic stem cells show multipotency and a capacity for self-renewal that enable these cells to regenerate damaged tissues. However, the in vitro proliferative ability of somatic stem cells is limited. The stem cells that exhibit pluripotency are embryonic stem (ES) cells, embryonic germ cells, embryonic carcinoma cells, and induced pluripotent stem (iPS) cells. Among these pluripotent stem cells, ES cells and iPS cells are expected to be a new potential source of cells for the treatment of many different degenerative diseases, including cardiovascular diseases, as a result of their capacity for self-renewal. The therapeutic effects of human ES cell–derived progeny have been reported in animal models for several diseases.1–5 iPS cells are derived from somatic cells by introducing defined reprogramming factors, and they have the ability to differentiate into various types of somatic cells (Figure 1). Figure 1. Generation of iPS cells from somatic cells. The reprogramming factors are introduced in vitro. The established iPS cells are able to differentiate into various cell types. ES cells, which are derived from the inner cell mass of mammalian blastocysts, have the ability to proliferate robustly while maintaining both their pluripotency and the ability to differentiate into cells of all 3 germ layers.6 Human ES cells were first derived …
The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis.

To the editor: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase in the B-cell receptor signaling pathway. In randomized trials, ibrutinib is effective as first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (compared with chlorambucil),[1][1]
Vision-based pose estimation and control of a model helicopter

In this paper, a vision system for pose estimation and stabilization control of a model helicopter has been proposed. This method consists of a pair of ground and onboard cameras, and it is used to estimate the full six degrees of freedom of the helicopter. The pose estimation algorithm is compared through simulation to some other feature based pose estimation methods and is shown to be less sensitive to feature detection errors. The proposed pose estimation algorithm and non-linear control techniques have been implemented on a remote controlled model helicopter.
Vector-valued image regularization with PDEs: a common framework for different applications

In this paper, we focus on techniques for vector-valued image regularization, based on variational methods and PDE. Starting from the study of PDE-based formalisms previously proposed in the literature for the regularization of scalar and vector-valued data, we propose a unifying expression that gathers the majority of these previous frameworks into a single generic anisotropic diffusion equation. On one hand, the resulting expression provides a simple interpretation of the regularization process in terms of local filtering with spatially adaptive Gaussian kernels. On the other hand, it naturally disassembles any regularization scheme into the smoothing process itself and the underlying geometry that drives the smoothing. Thus, we can easily specialize our generic expression into different regularization PDE that fulfill desired smoothing behaviors, depending on the considered application: image restoration, inpainting, magnification, flow visualization, etc. Specific numerical schemes are also proposed, allowing us to implement our regularization framework with accuracy by taking the local filtering properties of the proposed equations into account. Finally, we illustrate the wide range of applications handled by our selected anisotropic diffusion equations with application results on color images.
Parameterized Finite Difference Schemes for Plates: Stability, the Reduction of Directional Dispersion and Frequency Warping

In this paper, a simple family of explicit two-step finite difference methods for solving the classical equation of motion of a thin plate is examined. This family depends on several free parameters, and special attention is paid to the stability properties of these schemes, computational issues, and, in particular, the reduction of directional numerical dispersion. Numerical results, employing frequency warping techniques, are presented
Variation of resting energy expenditure after the first chemotherapy cycle in acute leukemia patients

Abstract Changes in resting energy expenditure (REE) of cancer patients vary depending on type of tumor, treatment time point and kind of treatment. Little is known about REE of acute leukemia adult patients after treatment, especially with results related to body weight or fat free mass (FFM). This study aimed to assess changes in REE of acute leukemia adult patients before and after the first remission induction. Evaluation of REE was performed by indirect calorimetry and predicted REE was calculated by Harris-Benedict equation. Weight and height were measured and compared to a control group of healthy individuals. FFM was assessed by bioelectrical impedance for adjusting REE values. We evaluated 18 patients and 26 healthy individuals. At diagnosis, patients presented REE, REE/weight, and REE/FFM higher than the controls. Reductions of REE, REE/weight, and REE/FFM were also observed in patients after the first cycle of chemotherapy. The predicted REE for the patients group showed significant lower value compared with measured REE. Before the first cycle of chemotherapy REE was increased but undergoes a reduction after treatment, reaching values similar to the controls. For predictive Harris-Benedict equation, stress factors should be added to avoid underestimation of REE before and after chemotherapy.
An investigation of iterative reconstruction strategies for lung lesion detection in SPECT

ROC and localization ROC (LROC) studies assessed whether modeling of the acquisition physics during the reconstruction process could improve detection of SLN in SPECT images. The radiotracer used was Tc-99m-labeled Neotect, and studies were run both with hybrid images and with phantom images. Iterative reconstruction strategies were defined with various combinations of attenuation correction (AC), scatter correction (SC), and resolution correction (RC). Results from both human and model observers indicate that AC degrades lung-lesion detection relative to applying RC alone. Subsequent studies with the model observer suggest that the relative effectiveness of the different iterative strategies will depend on observer knowledge of the mean normal background
The electrodynamics of sprites

A balloon campaign was conducted in summer, 1999, to measure the stratospheric electromagnetic fields associated with sprites. The balloon payloads were instrumented with electric field detectors, magnetometers, an upward looking photometer, and other instruments. Ground observations for detection of sprites included low light level TV (LLTV) observations from three sites, Jelm Mt., Wyoming, Bear Mt., South Dakota, and Yucca Ridge, Colorado. Flight 3 of the campaign flew from Ottumwa, Iowa at 00:39:32 UTC to 11:12:00 UTC on 08/21/99. A sprite at 0955:36.980 UTC produced a vertical electric field perturbation of ∼0.275 V/m that was similar in time profile to the light emission. There was also a positive azimuthal magnetic pulse of ∼3 nT.
Adherence of Aerornonas caviae to human cell lines Hep-2 and Caco-2

Adherence of Aeromonas caviae to HEp-2 and Caco-2 cell monolayers was investigated with 24 clinical isolates. Growth phase, temperature, multiplicity of infection and length of incubation affected adherence. Treatment of the bacteria with trypsin, sodium metaperiodate, mechanical shearing and the addition of cytochalasin B and cyclohex-imide to the monolayer significantly reduced the adherence capabilities of the strains investigated. The use of chloramphenicol to inhibit protein synthesis reduced the adhesive capabilities of bacteria grown in liquid medium and those subjected to mechanical shearing. Light microscopy, scanning and transmission electron microscopy were employed in the investigation of bacteria-bacteria and bacteria-monolayer interactions and indicated similarities with the aggregative adherence patterns of the Enterobacteriaceae. The presence of extracellular bacterial appendages and their correlation with increased adhesive capacity may indicate a role in the process of adherence.
Emotionally mediated synaesthesia

This study reports a synaesthete, GW, who experiences synaesthetic colours in response to a limited range of stimuli–namely those that have an emotional connotation. GW is significantly more consistent than a group of controls, and shows a Stroop‐like congruency effect when the text colour differs from that reported for her synaesthetic photisms. The names of people who are known personally to GW are more likely to induce a synaesthetic colour than names referring to people with whom she is not personally acquainted and other categories of word (including colour names themselves). This feature resembles a number of reports in the historical literature on synaesthesia. This is explained by the fact that these stimuli are more likely to elicit an emotional response. In support of this, other words that have an emotional connotation (e.g., “love”) have a tendency to elicit a synaesthetic response. The valence of the emotion (positive vs. negative) may have some role to play in determining the colour of the stimulus. It is concluded that emotion‐colour synaesthesia is a genuine, if unusual, form of synaesthesia.
Telomerase activity in pure pancreatic juice for the diagnosis of pancreatic cancer may be complementary to K-ras mutation.

BACKGROUND The usefulness of K-ras mutation in pancreatic juice for the diagnosis of pancreatic cancer is questionable. Telomerase is positive in pancreatic cancer but rarely in benign pancreatic diseases. We conducted this study to determine the usefulness of K-ras mutation and telomerase activity in pancreatic juice for the diagnosis of pancreatic cancer. METHODS Pancreatic juice collected during endoscopic retrograde cholangiopancreatography was examined in 31 patients: 12 with pancreatic cancer, 11 with chronic pancreatitis, and 8 control patients. The K-ras gene was detected by using the restriction fragment length polymorphism method. Telomerase activity was detected by using the telomeric repeat amplification protocol. RESULTS K-ras mutation was positive in 75% (9 of 12) of pancreatic cancers and in 27% (3 of 11) of cases of chronic pancreatitis but in none of the control patients. Telomerase activity was detected in 92% (11 of 12) of pancreatic cancers and in 18% (2 of 11) of cases of chronic pancreatitis. The diagnostic value in pancreatic cancer was comparable between K-ras mutation and telomerase when evaluated separately. However, by combining these 2 methods, the specificity rose to 100%. CONCLUSIONS For the diagnosis of pancreatic cancer, telomerase activity in pancreatic juice may possibly be complementary to K-ras mutation because it may decrease the rate of false-positive diagnosis.
Apoptosis of Bystander T Cells Induced by Human Immunodeficiency Virus Type 1 with Increased Envelope/Receptor Affinity and Coreceptor Binding Site Exposure

ABSTRACT Apoptosis of uninfected bystander CD4+ T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1) pathogenesis. The viral and host mechanisms that lead to bystander apoptosis are not well understood. To investigate properties of the viral envelope glycoproteins (Env proteins) that influence the ability of HIV-1 to induce bystander apoptosis, we used molecularly cloned viruses that differ only in specific amino acids in Env. The ability of these strains to induce bystander apoptosis was tested in herpesvirus saimiri-immortalized primary CD4+ T cells (CD4/HVS), which resemble activated primary T cells. Changes in Env that increase affinity for CD4 or CCR5 or increase coreceptor binding site exposure enhanced the capacity of HIV-1 to induce bystander apoptosis following viral infection or exposure to nonreplicating virions. Apoptosis induced by HIV-1 virions was inhibited by CD4, CXCR4, and CCR5 antibodies or by the CXCR4 inhibitor AMD3100, but not the fusion inhibitor T20. HIV-1 virions with mutant Envs that bind CXCR4 but are defective for CD4 binding or membrane fusion induced apoptosis, whereas CXCR4 binding-defective mutants did not. These results demonstrate that HIV-1 virions induce apoptosis through a CXCR4- or CCR5-dependent pathway that does not require Env/CD4 signaling or membrane fusion and suggest that HIV-1 variants with increased envelope/receptor affinity or coreceptor binding site exposure may promote T-cell depletion in vivo by accelerating bystander cell death.
A Frustrated Binding Interface for Intrinsically Disordered Proteins*

Background: Protein-protein interactions often involve intrinsically disordered protein domains. Results: The binding interface between two disordered protein domains is suboptimal, or frustrated, with regard to the energetics. Conclusion: The frustration likely results from the promiscuous binding behavior of these disordered domains. Significance: Suboptimal binding interfaces may be common among intrinsically disordered proteins with multiple binding partners. Intrinsically disordered proteins are very common in the eukaryotic proteome, and many of them are associated with diseases. Disordered proteins usually undergo a coupled binding and folding reaction and often interact with many different binding partners. Using double mutant cycles, we mapped the energy landscape of the binding interface for two interacting disordered domains and found it to be largely suboptimal in terms of interaction free energies, despite relatively high affinity. These data depict a frustrated energy landscape for interactions involving intrinsically disordered proteins, which is likely a result of their functional promiscuity.