Miracle-dz/UniFAR-FTUs huggingface dataset:
Image denoising substantially improves accuracy and precision of intravoxel incoherent motion parameter estimates

Applicability of intravoxel incoherent motion (IVIM) imaging in the clinical setting is hampered by the limited reliability in particular of the perfusion-related parameter estimates. To alleviate this problem, various advanced postprocessing methods have been introduced. However, the underlying algorithms are not readily available and generally suffer from an increased computational burden. Contrary, several computationally fast image denoising methods have recently been proposed which are accessible online and may improve reliability of IVIM parameter estimates. The objective of the present work is to investigate the impact of image denoising on accuracy and precision of IVIM parameter estimates using comprehensive in-silico and in-vivo experiments. Image denoising is performed with four different algorithms that work on magnitude data: two algorithms which are based on nonlocal means (NLM) filtering, one algorithm that relies on local principal component analysis (LPCA) of the diffusion-weighted images, and another algorithms that exploits joint rank and edge constraints (JREC). Accuracy and precision of IVIM parameter estimates is investigated in an in-silico brain phantom and an in-vivo ground truth as a function of the signal-to-noise ratio for spatially homogenous and inhomogenous levels of Rician noise. Moreover, precision is evaluated using bootstrap analysis of in-vivo measurements. In the experiments, IVIM parameters are computed a) by using a segmented fit method and b) by performing a biexponential fit of the entire attenuation curve based on nonlinear least squares estimates. Irrespective of the fit method, the results demonstrate that reliability of IVIM parameter estimates is substantially improved by image denoising. The experiments show that the LPCA and the JREC algorithms perform in a similar manner and outperform the NLM-related methods. Relative to noisy data, accuracy of the IVIM parameters in the in-silico phantom improves after image denoising by 76–79%, 79–81%, 84–99% and precision by 74–80%, 80–83%, 84–95% for the perfusion fraction, the diffusion coefficient, and the pseudodiffusion coefficient, respectively, when the segmented fit method is used. Beyond that, the simulations reveal that denoising performance is not impeded by spatially inhomogeneous levels of Rician noise in the image. Since all investigated algorithms are freely available and work on magnitude data they can be readily applied in the clinical setting which may foster transition of IVIM imaging into clinical practice.
Teaming Up? China, India and Brazil and the Issue of Benefit-Sharing from Genetic Resource Use

ABSTRACT This article focuses on an area that has not been systematically addressed but is of crucial importance to China, India and Brazil: the global governance of genetic resources. All three are biodiversity-rich and, ever since biotechnology promised to turn DNA into gold, have been significant players in the genetic-resources regime complex. Shortcomings notwithstanding, the establishment of a new access and benefit-sharing regime constitutes a rare instance where emerging countries have succeeded in becoming rule-makers of sorts. We analyse how these three countries have sought to pursue their interests in this area, especially after the extension of national sovereignty over previously ‘free’ genetic resources and the erection of a complex set of rules attempting to regulate access to and benefits from their utilisation from the early 1990s onwards. Despite presenting a generally unified front in international fora, their domestic implementation differs significantly and raises questions about the continuation of a common international position. The article adds to our understanding of emerging countries’ engagement with global governance by focusing on the concrete drivers and domestic processes that have motivated and shaped the agency of China, India and Brazil in this new policy regime.
Do zero and sign restricted SVARs identify unconventional monetary policy shocks in the euro area

This research re-examines the findings of the existing literature on the effects of unconventional monetary policy. It concludes that the existing estimates based on vector autoregressions in combination with zero and sign restrictions do not successfully isolate unconventional monetary policy shocks from other shocks impacting the euro area economy. In our research, we show that altering existing published studies by making the incorrect assumption that expansionary monetary shocks shrink the ECBâ€™s balance sheet or even ignoring all information about the stance of monetary policy results in the same shocks and, therefore, the same estimated responses of output and prices. As a consequence, it is implausible that the shocks previously identified in the literature are true unconventional monetary policy shocks. Since correctly isolating unconventional monetary policy shocks is a prerequisite for subsequently estimating the effects of unconventional monetary policy shocks, the conclusions from previous vector autoregression models are unwarranted. We show this lack of identification for different specifications of the vector autoregression models and different sample periods.
A Drosophila gustatory receptor required for the responses to sucrose, glucose, and maltose identified by mRNA tagging

In Drosophila, detection of tastants is thought to be mediated by members of a family of 68 gustatory receptors (Grs). However, only one receptor, Gr5a, has been associated with a sugar, and it appears to be activated specifically by trehalose. It is unclear whether other sugar receptors are activated by single or multiple sugars. Currently, no Grs are known to colocalize with Gr5a. Such Grs would be candidate sugar receptors because Gr5a-expressing cells function in the responses to attractive tastants. Here we use an “mRNA tagging” approach to identify Gr RNAs that are coexpressed with Gr5a. We found that all seven Grs most related to Gr5a (Gr64a-f and Gr61a) were expressed in Gr5a-expressing cells, whereas none of the other Grs examined were enriched in these Gr neurons (GRNs). We characterized the role of one Gr5a-related receptor, Gr64a, and found that it was required for the behavioral responses to glucose, sucrose, and maltose. Gr64a was required for GRN function because action potentials induced by these sugars were dependent on expression of Gr64a in GRNs. These data demonstrate that multiple Grs are coexpressed with Gr5a and that Drosophila Gr64a is required for the responses to multiple sugars.
What predicts suicide attempts in women with eating disorders?

Background. Suicide is a common cause of death in anorexia nervosa and suicide attempts occur often in both anorexia nervosa and bulimia nervosa. No studies have examined predictors of suicide attempts in a longitudinal study of eating disorders with frequent follow-up intervals. The objective of this study was to determine predictors of serious suicide attempts in women with eating disorders. Method. In a prospective longitudinal study, women diagnosed with either DSM-IV anorexia nervosa (n=136) or bulimia nervosa (n=110) were interviewed and assessed for suicide attempts and suicidal intent every 6–12 months over 8·6 years. Results. Fifteen percent of subjects reported at least one prospective suicide attempt over the course of the study. Significantly more anorexic (22·1%) than bulimic subjects (10·9%) made a suicide attempt. Multivariate analyses indicated that the unique predictors of suicide attempts for anorexia nervosa included the severity of both depressive symptoms and drug use over the course of the study. For bulimia nervosa, a history of drug use disorder at intake and the use of laxatives during the study significantly predicted suicide attempts. Conclusions. Women with anorexia nervosa or bulimia nervosa are at considerable risk to attempt suicide. Clinicians should be aware of this risk, particularly in anorexic patients with substantial co-morbidity.
Experience in simulation and measurement of GaN FET switching behavior

Due to their better figure of merits, gallium nitride field effect transistors (GaN FETs), when employed as the switching devices in power electronics applications, have better performance than conventional silicon metal-oxide-semiconductor field effect transistors (Si MOSFETs). One of the superiorities of GaN FETs is their ability to switch very fast, which results in low switching losses. However, the associated high di/dt and dv/dt can lead to severe parasitic effects in the circuit, impacting circuit operation. Therefore, the switching behavior of GaN FETs in a circuit should be investigated carefully with various circuit parasites taken into consideration. A simulation circuit model is particularly beneficial in addressing this point in that it enables observing the circuit behavior and identifying possibly existing problems before hardware implementation. In this paper, experience in building a GaN switching circuit prototype, measuring high speed switching signals, and establishing a simulation circuit model for the GaN switching circuit is presented. The prototype built involves a number of design considerations that are important in obtaining satisfactory switching behavior and measurement results. In particular, the board design conforms to certain layout rules that are especially critical for high speed switching circuits. A number of considerations about measurement and modeling are also discussed, and it turns out that probing position affects measurement fidelity enormously, and that a lumped simulation model taking critical trace inductances into consideration can predict GaN switching behavior to a reasonable extent.
High Incidence of Heterozygous ABCC8 and HNF1A Mutations in Czech Patients With Congenital Hyperinsulinism.

CONTEXT Congenital hyperinsulinism of infancy (CHI) represents a group of heterogeneous disorders characterized by oversecretion of insulin from pancreatic β-cells causing severe hypoglycemia. OBJECTIVE We studied the distribution of genetic causes of CHI in a Czech population. METHODS Countrywide collection of patients with CHI included 40 subjects (12 females, median age of diagnosis, 1 wk [interquartile range, 1-612 wk]). We sequenced the ABCC8, KCNJ11, GLUD1, GCK, HADH, UCP2, SLC16A1, HNF4A, and HNF1A genes and investigated structural changes in the ABCC8 gene. We functionally tested novel variants in the ABCC8 gene by Rb(86+) efflux assay and novel variants in the HNF1A gene by transcriptional activation and DNA-binding tests. RESULTS We found causal mutations in 20 subjects (50%): 19 carried a heterozygous mutation while one patient was homozygous for mutation in the ABCC8 gene. Specifically, we detected 11 mutations (seven novel) in ABCC8, one novel mutation in KCNJ11, five mutations (two novel) in HNF1A, two novel mutations in HNF4A, and one in GCK. We showed a decrease of activation by diazoxide in mutant KATP channels with novel ABCC8 variants by 41-91% (median, 82%) compared with wild-type (WT) channels and reduced transcriptional activity of mutant HNF1A proteins (2.9% for p.Asn62Lysfs93* and 22% for p.Leu254Gln) accompanied by no DNA-binding ability compared with WT HNF1A. CONCLUSION We detected a higher proportion of heterozygous mutations causing CHI compared with other cohorts probably due to lack of consanguinity and inclusion of milder CHI forms. Interestingly, HNF1A gene mutations represented the second most frequent genetic cause of CHI in the Czech Republic. Based on our results we present a genetic testing strategy specific for similar populations.
Zoledronic acid slows down rat primary chondrosarcoma development, recurrent tumor progression after intralesional curretage and increases overall survival

Chondrosarcoma is a difficult musculoskeletal tumor to treat. Surgical treatment leads to severe disability, with high rates of local recurrence and life threat. No adjuvant therapy is effective in differentiated chondrosarcomas. Bisphosphonates (BPs) are a class of molecules which is effective in malignant bone diseases. The aim of the present study was to determine the effects of zoledronic acid (ZOL) on chondrosarcoma tumor progression. ZOL was tested in vivo (s.c. 100 μg/kg, twice a week) in a rat chondrosarcoma model and in vitro (10−7–10−4 M) on cells derived from this model. Two types of animal models were assessed, the first simulated development after intralesional curettage, the second nonoperative development of the tumor. Cell proliferation, caspase‐1, ‐3 activities and cell cycle analysis were studied. The results revealed that ZOL slows down primary tumor development, tumor progression after intralesional curretage and increases overall survival. ZOL inhibits cell proliferation and increases cell death, with no significant variation of caspase‐1 and ‐3 activities and cell cycle profiles. The present study demonstrates for the first time that in addition to surgery, the therapy of chondrosarcoma with BPs might be beneficial. Because of these first results, new therapeutic approaches of chondrosarcoma must be considered, mainly for low grade chondrosarcoma when disabling operation is planned and when only intralesional resection can be undertaken. © 2006 Wiley‐Liss, Inc.
Long-term Outcomes of Penetrating Keratoplasty in Chronic and Delayed Mustard Gas Keratitis

Purpose: To report the long-term outcomes of penetrating keratoplasty (PKP) in war victims with chronic and delayed mustard gas keratitis. Methods: This noncomparative interventional case series includes patients with advanced chronic or delayed mustard gas keratitis who had undergone PKP from 1989 to 2006. Best-corrected visual acuity (BCVA), graft clarity, episodes of graft rejection, duration of steroid use, and complications were evaluated. Histopathologic features of excised corneal buttons were also evaluated. Results: Overall, 22 eyes of 19 patients underwent PKP. Mean age at the time of surgery was 41 ± 4.6 years (range, 36-54 years), and mean follow-up duration was 40.9 ± 48 months (range, 4-204 months). The graft remained clear in 17 (77.3%) eyes and failed in 5 (22.7%) eyes. Overall, 13 (59.1%) eyes experienced episodes of endothelial rejection, and 5 (22.7%) eyes had subepithelial immune rejection, 4 of which had simultaneous endothelial rejection. Fifteen (68.2%) eyes received topical steroids for >6 months. Fourteen (63.6%) eyes developed cataracts, leading to cataract extraction in 7 eyes. One eye developed steroid-induced glaucoma after multiple episodes of endothelial graft rejections. Mean preoperative BCVA was 1.92 ± 0.63 logMAR, which improved to 1.04 ± 0.65 logMAR (20/200) overall and 0.8 ± 0.3 logMAR (20/120) in eyes with clear grafts (P < 0.001). Main histopathologic features of excised corneal buttons included corneal thinning and ulceration, loss of keratocytes, acute and chronic inflammation, stromal vascularization, and degenerative sequelae of long-standing inflammation. Conclusions: PKP in chronic or delayed-onset mustard gas keratitis should be considered as a high-risk graft; however, with appropriate management, graft clarity and visual outcomes may be favorable.
Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.
Induced sputum and occupational diseases other than asthma

Purpose of reviewInduced sputum noninvasively provides information on cellular and soluble material from airways. It has been successfully applied for assessing airway inflammation in asthma and chronic obstructive pulmonary disease, producing reliable results comparable to biopsy and bronchoalveolar lavage. Induced sputum research in the field of occupational medicine has mainly focused upon occupational asthma, and less to other types of occupational diseases. Recent findingsParticulate size distribution in induced sputum samples points to accumulation over time, leading to the consideration that this measurement may serve as a time-dependent marker for biological monitoring. Qualitative analysis of chemical composition of induced sputum particles is well correlated to the chemical elements spectrum in bronchoalveolar lavage lung cells and in biopsy thin sections. T cell subsets in induced sputum can be used as a marker of granulomatosis in chronic beryllium disease. Cytokines retrieved from induced sputum samples in exposed workers show a differential pattern compared to nonexposed workers. SummaryInduced sputum is a well tolerated, noninvasive technique that is opening a new window in the field of occupational diseases of the lung and can be integrated into the well established criteria for diagnosing and monitoring these diseases, especially when invasive techniques are clinically contraindicated or impractical.
Drug survival of the first course of anti-TNF agents in patients with rheumatoid arthritis and seronegative spondyloarthritis: analysis from the MonitorNet database.

OBJECTIVES To compare drug survival of different anti-TNF drugs (infliximab, INF, etanercept, ETA, and adalimumab, ADA) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) by analysing data collected from an Italian multicenter observational cohort study. METHODS All patients with RA or SpA registered in the MonitorNet database who started their first course of anti-TNF therapy were included. Overall drug survival was measured, along with specific reasons of discontinuation (inefficacy or adverse events). A first set of analyses using RA as reference category assessed the relationship between diagnosis and drug survival. A second set of analyses stratified by diagnosis (RA and SpA) used INF as reference drug. Adjustment for confounders was performed. The results are presented as adjusted hazard ratios (adjHR) and 95% confidence intervals (95%CI). RESULTS 2640 RA patients and 1220 SpA patients with a median follow-up of 17 months (IQR 7.2-33.4) were included in the analyses. Patients with a diagnosis of SpA showed a lower risk of drug discontinuation with an adjHR (95%CI) of 0.81 (0.73, 0.90). In SpA, the subset of patients with ankylosing spondylitis (AS) showed the best survival on treatment. In RA, both ETA and ADA showed a significantly lower probability of withdrawal when compared to INF [adjHR (95%CI) 0.46 (0.38, 0.56) and 0.68 (0.57, 0.81), respectively]. Similar results were found in SpA. CONCLUSIONS Drug survival for SpA is longer than that in RA mainly due to the AS subgroup. In both RA and SpA, ETA and ADA showed a better retention on treatment when compared to INF.
An Individualized Conditional Survival Calculator for Patients with Rectal Cancer

BACKGROUND: Conditional survival estimates account for time survived since diagnosis to provide prognostic information for long-term cancer survivors. For rectal cancer, stage-related treatment (eg, neoadjuvant radiotherapy) affects pathologic stage and therefore stage-associated survival estimates. OBJECTIVES: The aim of this study is to estimate conditional survival for patients who have rectal cancer and to develop an interactive calculator to use for individualized patient counseling. PATIENTS: Patients with rectal adenocarcinoma were identified by using the Surveillance Epidemiology and End Results registry (1988–2002, N = 22,610). DESIGN: Cox regression models were developed to determine adjusted survival estimates (years 1–10) and used to calculate 5-year adjusted conditional survival. Models were built separately for no radiotherapy, preoperative radiotherapy, postoperative radiotherapy, and patients with stage IV disease. Covariates included age, sex, race, tumor grade, and type of surgery. An Internet-based conditional survival calculator was developed. RESULTS: Radiotherapy was given to 42.6% of patients (14.1% preoperative, 28.4% postoperative). Significant improvements in 5-year conditional survival were observed for all stages, with the exception of stage I because of the initial high survival probability at diagnosis. Patients with advanced stage had the greatest improvements in conditional survival, with 5-year absolute increases of 33% (stage IIIC) and 54% (IV). Other factors associated with conditional survival included sequence of radiotherapy and surgery, age, race, and tumor grade. The Internet-based conditional survival calculator can be accessed at www.mdanderson. org/rectalcalculator. LIMITATIONS: The data source used does not include information on chemotherapy treatment, change in staging after neoadjuvant treatment, or patient comorbidities. CONCLUSION: Conditional survival estimates improve over 5 years in patients who have rectal cancer; the greatest improvements are observed among patients with advanced stage disease. The conditional survival calculator is an individualized decision support tool that informs patients, who must make non-treatment-related life decisions, and their clinicians planning follow-up and surveillance.
Can Norm Theory Explain the Effects of Victim Age and Level of Physical Maturity on Perceptions of Child Sexual Abuse?

The present study examines the effects of victim age, victim physical maturity, and respondent gender on attributions toward victims, perpetrator, and the nonoffending members of the victim’s family in a hypothetical child sexual abuse (CSA) case. Participants read a brief CSA vignette in which the male perpetrator (a school caretaker) sexually abuses a student in the school changing rooms. The victim was depicted as either a 12- or 15-year-old girl who, in terms of physical maturity, was either pre- or postpubescent. Separate 2 × 2 × 2 ANOVAs were performed on the dependent variables. Results conformed broadly to the study’s predictions with younger victims being viewed more negatively than older victims and the victim’s physical appearance being viewed as more encouraging of CSA for the younger than for the older girl. Female participants were more likely to endorse the belief that the younger victim should have fought back and that the prepubescent 15-year-old victim should have fought back more than her postpubescent counterpart. While attributions toward the perpetrator and victim’s family did not differ across conditions for women, men tended to blame the perpetrator more when victims were younger and the family more when victims were less physically mature. Findings are discussed in relation to norm theory principles, just world theory, and the defensive attribution hypothesis.