Miracle-dz/UniFAR-FTUs huggingface dataset:
Combining multiparametric MRI with receptor information to optimize prediction of pathologic response to neoadjuvant therapy in breast cancer: preliminary results

Abstract Pathologic complete response following neoadjuvant therapy (NAT) is used as a short-term surrogate marker of eventual outcome in patients with breast cancer. Analyzing voxel-level heterogeneity in MRI-derived parametric maps, obtained before and after the first cycle of NAT (n=33), in conjunction with receptor status, may improve the predictive accuracy of tumor response to NAT. Toward that end, we incorporated two MRI-derived parameters, the apparent diffusion coefficient and efflux rate constant, with receptor status in a logistic ridge-regression model. The area under the curve (AUC) and Brier score of the model computed via 10-fold cross validation were 0.94 (95% CI: 0.85, 0.99) and 0.11 (95% CI: 0.06, 0.16), respectively. These two statistics strongly support the hypothesis that our proposed model outperforms the other models that we investigated (namely, models without either receptor information or voxel-level information). The contribution of the receptor information was manifested by an 8% to 15% increase in AUC and a 14% to 21% decrease in Brier score. These data indicate that combining multiparametric MRI with hormone receptor status has a high likelihood of improved prediction of pathologic response to NAT in breast cancer.
Investor Reaction to Accounting Misstatements Under IFRS: Australian Evidence

We examine the investor reaction to misstatement news for Australian listed firms for the period 2006 to 2013. There are 4.1% of firm years with misstatements and 79% of misstatements are initially disclosed only in the financial statements (stealth misstatements). We find no investor reaction for the average misstatement, reactions of between -2.3% and -2.8% (-1.5% and -1.7%) for misstatements that reduce prior-period earnings or equity (affect revenue), and reactions between -1.3% to -2.7% for nonstealth misstatements. The market reacts more negatively to nonstealth misstatements that reduce prior-period earnings or equity than to stealth ones.
Comparison of genomic damage caused by 5‐nitrofurantoin in young and adult mice using the in vivo micronucleus assay

The antibiotic 5‐nitrofurantoin (5‐NF) has been used widely for the treatment of urosepsis in children during the last 20 years. Recent experimentation suggests the need for reevaluating its genotoxic potential. Because of possible differences in the metabolism and clearance of 5‐NF in young and adult animals, we conducted a study to determine whether micronuclei caused by 5‐NF were age‐related. The in vivo micronucleus (MN) assay was performed on 3‐ and 8‐week‐old mice given single intraperitoneal injections of 5, 10, and 50 mg/kg 5‐NF. Blood samples from the tail vein were taken before injection (baseline) and at 48, 96, 168, and 336 hr (2 weeks) after the treatment. One thousand reticulocytes were analyzed for micronuclei from each animal. Compared to similar baseline values for young and adult mice, 5‐NF caused a significant increase in MN frequency in both age groups. The mean MN frequency in the young animals was higher than in the adult animals for each dose and sampling time. MN frequencies remained significantly elevated in young animals even 2 weeks after exposure to 5‐NF. The results of the study confirm the genotoxic potential of 5‐NF in young and adult animals, and indicate that young animals are more sensitive to the genotoxic effects of 5‐NF than adult mice and that the response in young mice persists for a significantly longer time. These findings may be related to poorly developed mechanisms of xenobiotic detoxification and renal elimination in young animals. Environ. Mol. Mutagen. , 2005. © 2005 Wiley‐Liss, Inc.
MR assessment of brain maturation: comparison of sequences.

PURPOSE To evaluate the role of short-inversion-time inversion-recovery (STIR) sequences in assessment of brain maturation. METHODS Twenty-seven infants and young children with normal neurologic development were examined by 1.5-T MR using a circularly polarized head coil. Axial T1-weighted and T2-weighted and spin-echo and STIR images were obtained. Signal intensity of different anatomic structures at individual sequences was classified relatively to reference sites and temporal sequence of signal intensity was observed. RESULTS Signal intensity changes on T1-weighted and T2-weighted spin-echo sequences occurred at ages described in various previous publications. On STIR images intensity changes became apparent at a time between T1-weighted and T2-weighted images. The advantages of the STIR sequence were improved assessment of myelination of subcortical cerebral white matter from 6 to 14 months and good contrast between white matter lesions and cerebrospinal fluid. CONCLUSION Our results suggest that from 0 to 6 months myelination can be assessed best using a combination of T1-weighted and T2-weighted images; from 6 to 14 months a combination of T2-weighted and STIR images seems to be advantageous; after 14 months the use of only T2-weighted sequences is sufficient. After 14 months STIR images may be useful in detecting small periventricular white matter lesions or in cases with retarded myelination and isointensity between gray matter and white matter.
Comparative Analysis of Light-Harvesting Antennae and State Transition in chlorina and cpSRP Mutants1[OPEN]

Comparative analysis of chlorina and cpSRP mutants provides the novel genetic evidence for the flexible organization of light-harvesting complexes and their dynamic and reversible allocation to the two photosystems. State transitions in photosynthesis provide for the dynamic allocation of a mobile fraction of light-harvesting complex II (LHCII) to photosystem II (PSII) in state I and to photosystem I (PSI) in state II. In the state I-to-state II transition, LHCII is phosphorylated by STN7 and associates with PSI to favor absorption cross-section of PSI. Here, we used Arabidopsis (Arabidopsis thaliana) mutants with defects in chlorophyll (Chl) b biosynthesis or in the chloroplast signal recognition particle (cpSRP) machinery to study the flexible formation of PS-LHC supercomplexes. Intriguingly, we found that impaired Chl b biosynthesis in chlorina1-2 (ch1-2) led to preferentially stabilized LHCI rather than LHCII, while the contents of both LHCI and LHCII were equally depressed in the cpSRP43-deficient mutant (chaos). In view of recent findings on the modified state transitions in LHCI-deficient mutants (Benson et al., 2015), the ch1-2 and chaos mutants were used to assess the influence of varying LHCI/LHCII antenna size on state transitions. Under state II conditions, LHCII-PSI supercomplexes were not formed in both ch1-2 and chaos plants. LHCII phosphorylation was drastically reduced in ch1-2, and the inactivation of STN7 correlates with the lack of state transitions. In contrast, phosphorylated LHCII in chaos was observed to be exclusively associated with PSII complexes, indicating a lack of mobile LHCII in chaos. Thus, the comparative analysis of ch1-2 and chaos mutants provides new evidence for the flexible organization of LHCs and enhances our understanding of the reversible allocation of LHCII to the two photosystems.
Heterodimers of the transcriptional factors NFATc3 and FosB mediate tissue factor expression for 15(S)-hydroxyeicosatetraenoic acid–induced monocyte trafficking

Tissue factor (TF) is expressed in vascular and nonvascular tissues and functions in several pathways, including embryonic development, inflammation, and cell migration. Many risk factors for atherosclerosis, including hypertension, diabetes, obesity, and smoking, increase TF expression. To better understand the TF-related mechanisms in atherosclerosis, here we investigated the role of 12/15-lipoxygenase (12/15-LOX) in TF expression. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major product of human 15-LOXs 1 and 2, induced TF expression and activity in a time-dependent manner in the human monocytic cell line THP1. Moreover, TF suppression with neutralizing antibodies blocked 15(S)-HETE–induced monocyte migration. We also found that NADPH- and xanthine oxidase–dependent reactive oxygen species (ROS) production, calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation, and interactions between nuclear factor of activated T cells 3 (NFATc3) and FosB proto-oncogene, AP-1 transcription factor subunit (FosB) are involved in 15(S)-HETE–induced TF expression. Interestingly, NFATc3 first induced the expression of its interaction partner FosB before forming the heterodimeric NFATc3–FosB transcription factor complex, which bound the proximal AP-1 site in the TF gene promoter and activated TF expression. We also observed that macrophages from 12/15-LOX−/− mice exhibit diminished migratory response to monocyte chemotactic protein 1 (MCP-1) and lipopolysaccharide compared with WT mouse macrophages. Similarly, compared with WT macrophages, monocytes from 12/15-LOX−/− mice displayed diminished trafficking, which was rescued by prior treatment with 12(S)-HETE, in a peritonitis model. These observations indicate that 15(S)-HETE–induced monocyte/macrophage migration and trafficking require ROS-mediated CaMKIV activation leading to formation of NFATc3 and FosB heterodimer, which binds and activates the TF promoter.
Cannabinoid receptor‐2 agonist inhibits macrophage induced EMT in non‐small cell lung cancer by downregulation of EGFR pathway

JWH‐015, a cannabinoid receptor 2 (CB2) agonist has tumor regressive property in various cancer types. However, the underlying mechanism by which it acts in lung cancer is still unknown. Tumor associated macrophage (TAM) intensity has positive correlation with tumor progression. Also, macrophages recruited at the tumor site promote tumor growth by enhancing epithelial to mesenchymal (EMT) progression. In this study, we analyzed the role of JWH‐015 on EMT and macrophage infiltration by regulation of EGFR signaling. JWH‐015 inhibited EMT in NSCLC cells A549 and also reversed the mesenchymal nature of CALU‐1 cells by downregulation of EGFR signaling targets like ERK and STAT3. Also, in vitro co‐culture experiments of A549 with M2 polarized macrophages provided evidence that JWH‐015 decreased migratory and invasive abilities which was proved by reduced expression of FAK, VCAM1, and MMP2. Furthermore, it decreased macrophage induced EMT in A549 by attenuating the mesenchymal character by downregulating EGFR and its targets. These results were confirmed in an in vivo subcutaneous syngenic mouse model where JWH‐015 blocks tumor growth and also inhibits macrophage recruitment and EMT at the tumor site which was regulated by EGFR pathway. Finally, JWH‐015 reduced lung tumor lesions in an in vivo tumorigenicity mouse model. These data confer the impact of this cannabinoid on anti‐proliferative and anti‐tumorigenic effects, thus enhancing our understanding of its therapeutic efficacy in NSCLC. Our findings open new avenues for cannabinoid receptor CB2 agonist‐JWH‐015 as a novel and potential therapeutic target based on EGFR downregulation mechanisms in NSCLC. © 2016 Wiley Periodicals, Inc.
Does the FEF25–75 or the FEF75 have any value in assessing lung disease in children with cystic fibrosis or asthma?

While the FEV1 had been recognized as an excellent indicator of disability, it is not very sensitive to early and mild disease. In cystic fibrosis (CF) small airway disease is believed to be one of the early hallmarks and indices such as the FEF25–75 and FEF75 have been proposed as sensitive markers of early disease. The site of early disease in asthma is not as well worked out. Recently a study of more than 20,000 spirometries found that neither of these indices added anything to the FEV1/FVC but that study was not disease specific and contained both adults and children and the adults were the most numerous. To see if this would be true in children, 1,175 spirograms from children 6 to 18 years of age with CF or asthma whose FEV1 and FVC were above the lower limit of normal were taken from sequential studies. The data expressed in z scores was plotted with either the FEF25–75 or FEF75 plotted against FEV1/FVC. In both diseases, but particularly in asthma, the FEV1/FVC was more likely to be abnormal than either of the other two indices for suggesting that for children, early, or mild disease will be more apparent using the FEV1/FVC than any other index. Pediatr Pulmonol. 2015; 50:863–868. © 2015 Wiley Periodicals, Inc.
Automated left ventricular segmentation in cardiac MRI

We present an automated left ventricular (LV) myocardial boundary extraction method. Automatic localization of the LV is achieved using a motion map and an expectation maximization algorithm. The myocardial region is then segmented using an intensity-based fuzzy affinity map and the myocardial contours are extracted by cost minimization through a dynamic programming approach. The results from the automated algorithm compared against the experienced radiologists using Bland and Altman analysis were found to have consistent mean bias of 7% and limits of agreement comparable to the inter-observer variability inherent in the manual method.
Interleukin-6-Related Genotypes, Body Mass Index, and Risk of Multiple Myeloma and Plasmacytoma

Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions −174, −572, and −597; one variable number of tandem repeats (−373 AnTn); and one SNP in the IL-6 receptor (IL-6rα) gene at position −358. The variant allele of the IL-6 promoter SNP −572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The −373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI ≥ 30 kg/m2) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of <25 kg/m2. These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2285–91)
Lapse‐and‐Reentry in Variable Annuities

Section 1035 of the current U.S. tax code allows policyholders to exchange their variable annuity policy for a similar product while maintaining tax&#8208;deferred status. When the variable annuity contains a long&#8208;term guarantee, this &#8220;lapse&#8208;and&#8208;reentry&#8221; strategy allows the policyholder to potentially increase the value of the embedded guarantee. We show that for a return&#8208;of&#8208;premium death benefit guarantee this is frequently optimal, which has severe repercussions for pricing. We analyze various policy features that may help mitigate the incentive to lapse and compare them regarding the insurer's average expense payments and their posttax utility to the policyholder. We find that a ratchet&#8208;type guarantee and a state&#8208;dependent fee structure best mitigate the lapse&#8208;and&#8208;reentry problem, outperforming the typical surrender schedule. Further, when accounting for proper tax treatment, the policyholder prefers a variable annuity with either of these three policy features over a comparable stock investment.
Microglia in human immunodeficiency virus‐associated neurodegeneration

Infection with the human immunodeficiency virus (HIV) is associated with a syndrome of cognitive and motor abnormalities that may develop in the absence of opportunistic infections. Neurons are not productively infected by HIV. Thus, one hypothesis to explain the pathophysiology of HIV‐associated dementia (HAD) suggests that signals released from other infected cell types in the CNS secondarily lead to neuronal injury. Microglia are the predominant resident CNS cell type productively infected by HIV‐1. Neurologic dysfunction in HAD appears to be a consequence of microglial infection and activation. Several neurotoxic immunomodulatory factors are released from infected and activated microglia, leading to altered neuronal function, synaptic and dendritic degeneration, and eventual neuronal apoptosis. This review summarizes findings from clinical/pathological studies, animal models, and in vitro models of HAD. Most of these studies support the hypothesis that altered microglial physiology is the nidus for a cascade of events leading to neuronal dysfunction and death. Several molecular mediators of neuronal injury in HAD that emanate from microglia have been identified, and strategies for altering the impact of these neurotoxins are discussed. GLIA 40:240–251, 2002. © 2002 Wiley‐Liss, Inc.
Renal Blood Oxygenation Level–Dependent Imaging: Contribution of R2 to R2* Values

ObjectivesThe aim of this study was to assess the impact of oral water and intravenous furosemide challenges on blood oxygenation level–dependent magnetic resonance imaging measurements in the kidney and to examine the contribution of R2 (=1/T2) to changes in R2* (=1/T2*). Materials and MethodsThis Health Insurance Portability and Accountability Act–compliant study had institutional review board approval, and written informed consent was obtained from all subjects. Nine healthy volunteers were imaged at 3 T on 2 visits. During each visit, a baseline fasting magnetic resonance acquisition was followed by a diuretic challenge: oral water load for the first visit and furosemide for the second. R2* and R2 values in the renal cortex and medulla were measured using multiple gradient echo and multiple spin echo sequences, respectively, and R2’ values were computed as R2’ = R2* − R2. Timed urinary output was also measured. ResultsAveraged across all subjects, the R2* response to furosemide was greater than to water and greater in the medulla than the cortex. The mean R2 responses exhibited the same trends but were uniformly smaller than the mean R2* responses. The peak changes in R2* and R2 appeared, on average, 10 to 14 minutes before peak urinary output. The median percentage contribution of R2 to R2* changes was 16% in the medulla after both challenges. In the cortex, the median contribution was 48% after water load and 58% after furosemide challenge. ConclusionsThe contributions of R2 to R2* changes after water load and furosemide challenge are not negligible, especially in the renal cortex. In routine clinical practice, R2* could be used alone as a rough surrogate for R2’ in the medulla. However, in the cortex, both R2 and R2* should be measured to obtain accurate values of R2’.
Animal and culture models of glaucoma for studying neuroprotection.

PURPOSE Neuroprotection aims to treat nervous system disease by maintaining the health and function of neurons. The final proof of the neuroprotective strategy relies on randomized, controlled clinical trials, but the choice of which agents to study for these trials depends on studies in the laboratory using culture and animal models. Most culture models for studying ocular neuroprotection use retinal cells, and a range of mechanisms can be studied in culture, e.g. axotomy and serum or growth factor deprivation. METHODS A variety of animal models are available for studying neuroprotection as possible therapy for glaucomatous optic neuropathy. Those most closely related to glaucoma are probably associated with moderate elevation of the intraocular pressure to levels similar to those seen in patients with untreated glaucomatous optic neuropathy. CONCLUSIONS Care should be taken when applying the results of these models to humans, and there is no single criterion for deciding which culture or animal model is most relevant to the clinical situation. The most important feature is whether the models results correlate with clinical results, and this information will only become available over time, as randomized clinical trials are completed. Eur J Ophthalmol 2001; 11 (Suppl 2): S23-S29.
Wafer level encapsulation process for LED array packaging

Solid-state lighting (SSL) using high brightness light emitting diodes (HB-LEDs) is the emerging trend for general lighting applications. It is expected a substantial portion of conventional incandescent and fluorescent lighting will be replaced by SSL in the next 5-10 years. There are two major factors controlling the propagation of HB-LEDs for SSL applications. One is the optoelectronic efficiency and the other is the cost. Both factors are closely related to the packaging of LEDs. Currently most LEDs are packaged on an individual component basis. Such a component level packaging process has relatively low throughput. Consequently it is more difficult to implement automation for large scale mass production, which is a critical element for low cost manufacturing. Therefore, a more efficient packaging process is in demand in the LED industry. In the present study, a wafer level encapsulation process for LED array packaging is developed. The silicon wafer is pre-fabricated with a pattern of grooves which serve as stoppers for epoxy flow in the subsequent encapsulation process. Epoxy encapsulant is dispensed from a syringe onto the wafer, and then is cured by UV light to complete the encapsulation process. This process can be easily automated and, hence, may increase the production throughput and reduce the manufacturing cost of LED packaging. In order to optimize the quality of this newly developed encapsulation process, there are several design and processing considerations to be investigated. These include the volume of encapsulant, the geometry of grooves, and some epoxy dispensing and curing parameters. A prototype with encapsulated LED arrays on a silicon wafer will be illustrated. Detailed discussion on those critical processing parameters will be given.
Analysis and Optimization of the Acquisition Times in the Magnetic Resonance Imaging

The main purpose of this work is to analyze the magnetic resonance imaging (MRI) methodologies used in noninvasive clinical investigation, with the aim of reducing the time of acquisition by assuring a good quality of the images. This objective is of fundamental importance to both increase the number of clinical tests produced with this equipments and to reduce the radiation doses in the patients. For this purpose the parameters influencing the time acquisition and the signal-to-noise ratio (SNR) were investigated and a software platform to optimize the imaging time acquisition was developed. This work was carried out in collaboration with Martina Franca (Italy) Hospital. Tanks to the staff of this sanitary structure it has been possible to get the necessary material for the correct development of the simulation algorithm and the sample images on which the algorithm has been applied and verified.