Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual EGFR inhibition in combination with anti-VEGF treatment in colorectal cancer

Preclinical studies demonstrate that epidermal growth factor receptor (EGFR) signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic. We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with metastatic colorectal cancer was analyzed for safety and antitumor activity. Forty-one patients with heavily pretreated metastatic colorectal cancer received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (68%), hypomagnesemia (37%), and fatigue (15%). Thirty of 34 patients (88%) treated at the full FDA-approved doses of all three drugs tolerated treatment without drug-related dose-limiting effects. Eleven patients (27%) achieved stable disease (SD) ≥6 months and three (7%) achieved a partial response (PR) (total SD>6 months/PR= 14 (34%)). Of the 14 patients with SD≥6 months/PR, eight (57%) had received prior sequential bevacizumab and cetuximab, two (5%) had received bevacizumab and cetuximab concurrently, and four (29%) had received prior bevacizumab but not cetuximab or erlotinib (though three had received prior panitumumab). The combination of bevacizumab, cetuximab, and erlotinib was well tolerated and demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer.
THE AU MIC DEBRIS DISK: FAR-INFRARED AND SUBMILLIMETER RESOLVED IMAGING

We present far-infrared and submillimeter maps from the Herschel Space Observatory and the James Clerk Maxwell Telescope of the debris disk host star AU Microscopii. Disk emission is detected at 70, 160, 250, 350, 450, 500, and 850 μm. The disk is resolved at 70, 160, and 450 μm. In addition to the planetesimal belt, we detect thermal emission from AU Mic’s halo for the first time. In contrast to the scattered light images, no asymmetries are evident in the disk. The fractional luminosity of the disk is 3.9 × 10 − 4 ? > and its milimeter-grain dust mass is 0.01 M ⨁ ? > (±20%). We create a simple spatial model that reconciles the disk spectral energy distribution as a blackbody of 53 ± 2 K (a composite of 39 and 50 K components) and the presence of small (non-blackbody) grains which populate the extended halo. The best-fit model is consistent with the “birth ring” model explored in earlier works, i.e., an edge-on dust belt extending from 8.8 to 40 AU, but with an additional halo component with an r − 1.5 ? > surface density profile extending to the limits of sensitivity (140 AU). We confirm that AU Mic does not exert enough radiation force to blow out grains. For stellar mass-loss rates of 10–100 times solar, compact (zero porosity) grains can only be removed if they are very small; consistently with previous work, if the porosity is 0.9, then grains approaching 0.1 μm can be removed via corpuscular forces (i.e., the stellar wind).
Dynamic risk stratification system in post‐lobectomy low‐risk and intermediate‐risk papillary thyroid carcinoma patients

The dynamic risk stratification (DRS) and its current definition of each response‐to‐therapy category in post‐lobectomy papillary thyroid carcinoma (PTC) patients have not been well studied. This study aimed to validate the DRS system and to investigate useful thyroglobulin (Tg) or anti‐Tg antibody (Ab)‐related parameters in defining each response‐to‐therapy category.
Wearable health information systems intermittent discontinuance: A revised expectation-disconfirmation model

Purpose Wearable health information systems open up a new era for personal health self-management, and bring about disruptive changes to individual lives. However, current studies on information systems post-adoptive behavior primarily focused on either continuance or discontinuance, neglecting the mutual transformation process between IS usage and rejection behavior. Such state is expressed as intermittent discontinuance in the current study. By revising and extending the Expectation-Disconfirmation Model, this study tires to understand the factors affecting information system intermittent discontinuance in the context of wearable eHealth. Design/methodology/approach This study proposes a revised expectation-disconfirmation model by incorporating four new theoretical constructs, i.e., neutral disconfirmation, attitudinal ambivalence, neutral satisfaction, and intermittent discontinuance. An online survey was used to validate the research model, and 428 wearable health device users were recruited in this .
Effect of quercetin on the number of blastomeres, zona pellucida thickness, and hatching rate of mouse embryos exposed to actinomycin D: An experimental study

Background: Quercetin is a flavonoid with the ability to improve the growth of embryos in vitro, and actinomycin D is an inducer of apoptosis in embryonic cells. Objective: The aim was to evaluate the effect of quercetin on the number of viable and apoptotic cells, the zona pellucida (ZP) thickness and the hatching rate of preimplantation embryos exposed to actinomycin D in mice. Materials and Methods: Two-cell embryos were randomly divided into four groups (Control, Quercetin, actinomycin D, and Quercetin + actinomycin D group). Blastocysts percentage, hatched blastocysts, and ZP thickness of blastocysts was measured. The number of blastomeres was counted by Hoechst and propidium iodide staining and the apoptotic cells number was counted by TUNEL assay. Results: The results showed that the use of quercetin significantly improved the growth of embryos compared to the control group (p=0.037). Moreover, quercetin reduced the destructive effects of actinomycin D on the growth of embryos significantly (p=0.026). Conclusion: quercetin may protect the embryos against actinomycin D so that increases the number of viable cells and decreases the number of apoptotic cells, which can help the expansion of the blastocysts, thinning of the ZP thickness and increasing the hatching rate in mouse embryos.
Evaluation of an educational, theater-based intervention on attitudes toward organ donation in Risaralda, Colombia

Introduction: The shortage of organs for transplantation is a worldwide problem and the main cause is the refusal of family members to donate. Consent to donate is influenced by many factors and educational interventions are strongly recommended. Objective: To evaluate the impact of an educational, theaterbased strategy on the attitudes toward organ donation. Methods: This study employed an intervention using theater as the central tool. The impact of this intervention on the intention to donate was assessed through a controlled, prospective, nonrandomized designed study. The sample consisted of 1,038 people. All the participants answered a survey that asked about sex, age and intent to donate. Afterward, one portion of the sample was exposed to the play, The Gift of Life, and a subsequent discussion forum that was guided by experts. The same survey was administered again after the intervention. Results: Before the intervention, donation attitudes were positive in 68.3% of the responses, negative in 6.8% and uncertain in 24.9%. Females showed a greater intent to donate while age had no apparent influence on the donation decision. Those exposed to the intervention were found to be more likely to donate and show a favorable change in attitude toward donation than those who were not exposed to the intervention. Conclusion: An educational intervention using theater is an effective tool to generate a short-term change in the intent to donate. Educational strategies should be employed to increase the rates of organ donation.
Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds

Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.
Mycobacterium bovis BCG recADeletion Mutant Shows Increased Susceptibility to DNA-Damaging Agents but Wild-Type Survival in a Mouse Infection Model

ABSTRACT Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxifies reactive oxygen species, and DNA repair systems, which repair damage resulting from oxidative stress. To (i) determine the relative importance of the DNA repair system when oxidative stress is encountered by theMycobacterium tuberculosis complex during infection of the host and to (ii) provide improved mycobacterial hosts as live carriers to express foreign antigens, the recA locus was inactivated by allelic exchange in Mycobacterium bovisBCG. The recA mutants are sensitive to DNA-damaging agents and show increased susceptibility to metronidazole, the first lead compound active against the dormant M. tuberculosis complex. Surprisingly, the recAgenotype does not affect the in vitro dormancy response, nor does the defect in the DNA repair system lead to attenuation as determined in a mouse infection model. The recA mutants will be a valuable tool for further development of BCG as an antigen delivery system to express foreign antigens and as a source of a genetically stable vaccine against tuberculosis.
Realistic modeling of deep brain stimulation implants for electromagnetic MRI safety studies

We propose a framework for electromagnetic (EM) simulation of deep brain stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of a DBS patient using post-operative head and neck computed tomography (CT) images stitched together into a ‘virtual CT’ image covering the entire length of the implant. The body was modeled as homogeneous. The implant path extracted from the CT data contained self-intersections, which we corrected automatically using an optimization procedure. Using the CT-derived DBS path, we built a model of the implant including electrodes, helicoidal internal conductor wires, loops, extension cables, and the implanted pulse generator. We also built four simplified models with straight wires, no extension cables and no loops to assess the impact of these simplifications on safety predictions. We simulated EM fields induced by the RF birdcage body coil in the body model, including at the DBS lead tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the robustness of our simulation results by systematically varying the EM properties of the body model and the position and length of the DBS implant (sensitivity analysis). The topology correction algorithm corrected all self-intersection and curvature violations of the initial path while introducing minimal deformations (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution grid) ranged from 12.8 kW kg−1 (full model, helicoidal conductors) to 43.6 kW kg−1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg−1 (full model, straight conductors) to 73.8 kW kg−1 (no loops, straight conductors) at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak SAR with respect to the conductivity ranged between 18% and 30%. Variability with respect to the position and length of the DBS implant ranged between 9.5% and 27.6%.
Use of Common Medications and Breast Cancer Risk

Prescription and over-the-counter medications are widely used in the United States and many western countries. More than two-thirds of women ages >45 years, who are at greatest risk for breast cancer, take prescription medication. In light of the ubiquitous nature of medication use and the fact that breast cancer remains the most common cancer in women, research on the role of medication use in breast cancer etiology is warranted. We summarize the epidemiologic evidence on the association between breast cancer risk and use of common medications, including antibiotics, antidepressants, statins, antihypertensives, and nonsteroidal anti-inflammatory drugs. Overall, there is little evidence that would implicate the use of antibiotics, antidepressants, statins, and antihypertensives in the etiology of breast cancer. Although several prospective studies and a randomized low-dose aspirin chemoprevention trial have not shown lower risk of breast cancer among aspirin users, most studies that have examined the potential chemoprotective effect of nonsteroidal anti-inflammatory drugs have shown significant risk reductions for regular and prolonged use of these drugs. The existing literature on the role of medication use in breast carcinogenesis is complicated. Interpretation of the evidence is hampered due to major methodologic differences across studies, including exposure assessment, exposure classification, and adjustment for potential confounding variables. These differences largely stem from the fact that the majority of articles on this topic represent secondary data analyses from studies with inadequate information on exposure or confounders. Thus, future epidemiologic studies specifically designed to study these ubiquitous and biologically plausible exposures are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1564–95)
The effects of bevacizumab treatment in a rat model of retinal ischemia and perfusion injury

Purpose To create a model of an ischemic retina with temporary ischemia and reperfusion (IR) and to examine the possible antiapoptotic and neurodegenerative effects of a vascular endothelial growth factor (VEGF) antagonist. Methods Three groups were formed. Rats were subjected to continued ischemia for 45 min, and then reperfusion was allowed for 2 days. For the first group, ischemia was induced, but an anti-VEGF agent was not administered. For the second group, 2 days before ischemia, 0.005 ml (0.125 mg) of bevacizumab was administered intravitreally, and then the ischemic model was created. The last group’s intraocular pressure was not increased as in the control group, and only a cannula was introduced into the anterior chamber through the cornea. Six animals from each group were subjected to histomorphometry, and four were subjected to immunohistochemical and histopathologic examinations. For a histomorphometric examination, the number of cells in the retinal ganglion cell (RGC) layer was counted using the optical dissector method. For immunohistochemistry, the vascular endothelial growth factor receptor-2 (VEGFR-2) levels and apoptosis were examined in the retinal and choroidal tissue. Results It was observed that in an IR injury, bevacizumab reduces the death and apoptosis of cells in the RGC layer. It was also identified that although bevacizumab is a large molecule, the agent affects the choroid and reduces the amount of VEGFR-2 in this tissue. Conclusions IR may be used as a model of ischemic retinopathy that includes VEGF-dependent vascular permeability and neurodegeneration. Although VEGF is a neurotrophic molecule, in IR injury, treatment with bevacizumab, which is an anti-VEGF agent, decreases apoptosis, showing that excess function of this molecule can be hazardous.
Constitutive modeling of fabric anisotropy of sand

Recent laboratory investigations indicate that the stress-strain-strength responses of loose sands are appreciably affected by the fabric orientation of the soil with respect to the frame of principal stresses.A sand specimen exhibiting a dilative response during triaxial compression may show a contractive response during triaxial extension under otherwise identical conditions.A plasticity constitutive model for simulating inherently anisotropic sand behavior is presented.A second-order symmetric fabric tensor is defined to describe the material inherent anisotropy.The location of the critical state line is not fixed but modified to be a function of the anisotropic state variable,which is a scalar defined in terms of a joint invariant of the fabric tensor and the stress tensor.The plastic modulus is also modified to be dependent on the anisotropic state variable.By these two modifications,an existing bounding surface model can successfully simulate both the contractive and dilative responses of sand over a wide range of variations in stress and density.
Expression and Function of IL12/23 Related Cytokine Subunits (p35, p40, and p19) in Giant-Cell Arteritis Lesions: Contribution of p40 to Th1- and Th17-Mediated Inflammatory Pathways

Background Giant-cell arteritis (GCA) is considered a T helper (Th)1- and Th17-mediated disease. Interleukin (IL)-12 is a heterodimeric cytokine (p35/p40) involved in Th1 differentiation. When combining with p19 subunit, p40 compose IL-23, a powerful pro-inflammatory cytokine that maintains Th17 response. Objectives The aims of this study were to investigate p40, p35, and p19 subunit expression in GCA lesions and their combinations to conform different cytokines, to assess the effect of glucocorticoid treatment on subunit expression, and to explore functional roles of p40 by culturing temporal artery sections with a neutralizing anti-human IL-12/IL-23p40 antibody. Methods and results p40 and p19 mRNA concentrations measured by real-time RT-PCR were significantly higher in temporal arteries from 50 patients compared to 20 controls (4.35 ± 4.06 vs 0.51 ± 0.75; p < 0.0001 and 20.32 ± 21.78 vs 4.17 ± 4.43 relative units; p < 0.0001, respectively). No differences were found in constitutively expressed p35 mRNA. Contrarily, p40 and p19 mRNAs were decreased in temporal arteries from 16 treated GCA patients vs those from 34 treatment-naïve GCA patients. Accordingly, dexamethasone reduced p40 and p19 expression in cultured arteries. Subunit associations to conform IL-12 and IL-23 were confirmed by proximity-ligation assay in GCA lesions. Immunofluorescence revealed widespread p19 and p35 expression by inflammatory cells, independent from p40. Blocking IL-12/IL-23p40 tended to reduce IFNγ and IL-17 mRNA production by cultured GCA arteries and tended to increase Th17 inducers IL-1β and IL-6. Conclusion IL-12 and IL-23 heterodimers are increased in GCA lesions and decrease with glucocorticoid treatment. p19 and p35 subunits are much more abundant than p40, indicating an independent role for these subunits or their potential association with alternative subunits. The modest effect of IL-12/IL-23p40 neutralization may indicate compensation by redundant cytokines or cytokines resulting from alternative combinations.
Assessment of the efficiency of essential oils in the preservation of postharvest papaya in an antimicrobial packaging system Avaliação da eficiência de óleos essenciais na preservação pós-colheita de mamão mediante um sistema de embalagem antimicrobiana

Summary Rot and damage caused by post-harvest phytopathogenic fungi affect fruit quality. Essential oils (EO) are considered as an alternative to fungicides. Postharvest diseases of fruits may also be controlled by the bagging approach and the use of antimicrobial packaging. Based on the beneficial properties of EO and the concepts of bagging and antimicrobial packaging, this study aimed to develop sachets containing EO to be used as part of an antimicrobial packaging system. The activities of oregano, cinnamon and lemon grass EO were evaluated testing the sachets in vitro against the phytopathogenic fungi Alternaria alternata, Fusarium semitectum, Lasiodiplodia theobromae and Rhizopus stolonifer. The effects of the sachets on the microbiological and physicochemical parameters of post-harvest papaya were also evaluated. Both pure and sachet-incorporated EO showed antifungal activity in vitro against all tested fungi. For papaya, sachets containing cinnamon, oregano and lemon grass showed a significant reduction in the growth of mesophilic aerobic bacteria, yeasts and mould, with the cinnamon sachet causing the greatest reduction in microorganisms at the end of the storage time. Physicochemical parameters of papaya, such as weight loss, colour, firmness, total soluble solids/titratable acidity ratio and pH were not significantly altered by the presence of EO sachets, thus not affecting the natural ripening process of the papaya.
Acetyl-CoA promotes glioblastoma cell adhesion and migration through Ca2+–NFAT signaling

Here, Lee et al. investigated the molecular mechanisms by which acetyl-CoA production impacts gene expression and how acetyl-CoA promotes malignant phenotypes. Their findings show that acetyl-CoA can enhance H3K27ac in a locus-specific manner and that expression of cell adhesion genes is driven by acetyl-CoA in part through activation of Ca2+–NFAT signaling.
Aberrant DNA Methylation of SOCS1 Gene is Not Associated with Resistance to Imatinib Mesylate among Chronic Myeloid Leukemia Patients.

BACKGROUND In exploring the cause of Imatinib Mesylate (IM) resistance among Chronic Myeloid Leukemia (CML) patients who do not harbor BCR-ABL dependent mechanism, BCR-ABL independent pathways are the most probable pathways that should be explored. In BCR-ABL independent pathway, SOCS1 plays an important role as it helps in regulating optimal JAK/STAT activity. OBJECTIVE To identify the association of SOCS1 gene hypermethylation in mediating IM Resistance. METHOD The SOCS1 promoter methylation level of 92 BCR-ABL non mutated IM resistant CML patients, 83 IM good response CML patients and 5 normal samples from healthy individuals were measured using Methylation Specific-High Resolution Melt (MS-HRM) analysis. RESULTS Both primers used to amplify promoter region from -333 to -223 and from -332 to -188 showed less than 10% methylation in all CML and normal samples. Consequently, there was no significant difference in SOCS1 promoter methylation level between IM resistant and IM good response patients. CONCLUSION SOCS1 promoter methylation level is not suitable to be used as one of the biomarkers for predicting the possibility of acquiring resistance among CML patients treated with IM.