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Several similarity/diversity measures for data mining, chemometrics, and chemoinformatics are presented and discussed toward the different data they are applied to. After a short presentation of the axioms for dissimilarity and similarity functions, their relationships and the required data pretreatment, the theoretical definitions and formulas of distance and similarity measures for real‐valued, binary, ranked, frequency, and mixed‐type data are provided along with the main concepts on distances between sets and meta‐distances. Simple examples of calculation are given and extended comparisons are performed on the distances defined for real valued and binary data.

A recurrent mutation in FOXL2 (c.402C>G; p.C134W) is present in over 95% of adult-type granulosa cell tumours (AGCTs). In contrast, various loss-of-function mutations in FOXL2 lead to the development of blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). BPES is characterised by an eyelid malformation often accompanied with primary ovarian insufficiency. Two recent studies suggest that FOXL2 C402G is a gain- or change-of-function mutation with altered DNA-binding specificity. Another study proposes that FOXL2 C402G is selectively targeted for degradation, inducing somatic haploinsufficiency, suggesting its role as a tumour suppressor. The latter study relies on data indicative of an FOXL2 allelic imbalance in AGCTs. Here we present RNA-seq data as genetic evidence that no real allelic imbalance is observed at the transcriptomic level in AGCTs. Additionally, there is no loss of protein expression in tumours harbouring the mutated allele. These data and other features of this mutation compared to other oncogenes and tumour suppressor genes argue strongly against FOXL2 being a tumour suppressor in this context. Given the likelihood that FOXL2 C402G is oncogenic, targeting the variant protein or its downstream consequences is the most viable path forward to identifying an effective treatment for this cancer. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background The novel coronavirus disease‐2019 (COVID‐19) caused a sudden and unexpected increase in the number of hospital admissions and deaths worldwide. The impact of social distancing on blood stocks was significant. Data on the use of blood products by patients with COVID‐19 are scarce. Material and methods A retrospective observational study was conducted by analysing the medical records of 3014 hospitalized COVID‐19 patients in 16 Brazilian hospitals. Individual data related to clinical, laboratory and transfusion characteristics and outcomes of these patients were collected. Patients characteristics association with mortality and transfusion need were tested independently by logistic regression models. Results Patients mean age was 57·6 years. In 2298 (76·2%) patients, there was an underlying clinical comorbidity. A total of 1657 (55%) patients required admission to intensive care unit (ICU), and 943 (31%) patients required ventilatory support and orotracheal intubation (OTI). There was a total of 471 (15·6%) deaths among all patients. 325 patients (10·7%) required blood transfusion; 3187 blood products were transfused: 1364 red blood cells in 303 patients, 1092 platelet units in 78 patients, 303 fresh frozen plasma in 49 patients and 423 cryoprecipitates in 21 patients. The mortality among patients who received transfusion was substantially higher than that among the total study population. Conclusion Need for transfusion was low in COVID‐19 patients, but significantly higher in patients admitted to ICU and in those who needed OTI. Knowledge of the transfusion profile of these patients allows better strategies for maintaining the blood stocks of hospitals during the pandemic.

Osteogenesis imperfecta (OI) type VIII (OMIM: 610915) is a rare autosomal recessive disorder characterized by white sclerae, severe growth deficiency, and bone fragility. This condition results from pathogenic variants of P3H1, a gene that codes for P3H1, an important protein involved in the prolyl-3-hydroxylation complex required for collagen type I folding. Here, we described a woman with OI type VIII due to a homozygous mutation of c.1914+1G>C (NM_001243246.1) in P3H1 and retinal detachment. We compared our case to five severe OI and retinal detachment cases reported in the literature. The only case previously reported with a molecular diagnosis had a similar mutation in P3H1 c.1914+1G>A and a giant retinal detachment. We suggest that individuals with OI type VIII should be submitted to careful fundoscopic examination.

Here we report the case of successful immune tolerance induction in a living‐donor kidney transplant recipient remotely treated with autologous bone marrow‐derived mesenchymal stromal cells (MSC). This case report, which to the best of our knowledge is the first in the world in this setting, provides evidence that the modulation of the host immune system with MSC can enable the safe withdrawal of maintenance immunosuppressive drugs while preserving optimal long‐term kidney allograft function., This report provides the evidence that autologous BM‐MSC infusion induces a pro‐tolerogenic immune environment, thus allowing complete discontinuation of antirejection drugs in kidney transplantation

FOXL2 and ESR2 are key transcriptional regulators in ovarian granulosa cells. To explore their transcriptional roles and their interplay, we have depleted Foxl2 and Esr2 in mouse primary granulosa cells to assess their ability to bind their targets and/or to modulate gene expression and cellular functions. We show that FOXL2 is involved in a large number of regulatory actions essential for the maintenance of granulosa cell fate. A parallel ChIP-seq analysis showed that FOXL2 mainly binds to sites located in intergenic regions quite far from its targets. A bioinformatic analysis demonstrated that FOXL2-activated genes were enriched in peaks associated with the H3K27ac mark, whereas FOXL2-repressed genes were not, suggesting that FOXL2 can activate transcription through binding to enhancer sites. We also identified about 500 deregulated genes upon Esr2 silencing, of which one third are also targets of FOXL2. We provide evidence showing that both factors modulate, through a coherent feed-forward loop, a number of common targets. Many of the FOXL2/ESR2 targets are involved in cell motility and, consistently, granulosa cells depleted for either Foxl2 or Esr2 exhibit decreased migration, invasion and adhesion. This effect is paralleled by the depletion of their target Phactr1, involved in actin cytoskeleton dynamics. Our analysis expands the number of direct and indirect transcriptional targets of both FOXL2 and ESR2, which deserve investigation in the context of adult-type granulosa cell tumors whose molecular diagnostic hallmark is the presence of the C134W FOXL2 pathogenic variant.

Several studies have shown a significant increase in wheat (Triticum aestivum L.) grain yield (GY) worldwide during the 20th century as a result of genetic and environmental improvement. The objective of this study was to measure the genetic gains achieved in a wheat breeding program maintained by the Central Cooperative of Agricultural Research (COODETEC) in Brazil through the annual evaluation of lines in multienvironment trials. The dataset was composed of 836 advanced trials and was evaluated in 40 representative locations to assess the value for cultivation and use (VCU) regions in the south, southeast, and central-west areas of the country from 2004 to 2013. Each trial consisted of 25 treatments (lines + checks) in a randomized complete block design with three replicates. A linear mixed model was fitted to predict the genetic values of each genotype per year and a restricted maximum likelihood algorithm to estimate the variance components. These genetic values were used to compute the genetic gain over the years. The overall estimated genetic gain of the breeding program was 61.59 kg ha⁻¹ yr⁻¹ (1.68% yr⁻¹) for GY, although it was partially counterbalanced by the estimated negative environmental effects. The genetic gain per VCU region ranged from 31.38 (VCU 4) to 115.33 kg ha⁻¹ yr⁻¹ (VCU 1). After accounting for the environmental changes over years, the yield gain was 39.40 kg ha⁻¹ yr⁻¹ (1.10% yr⁻¹), ranging from −0.82 (VCU 3) to 3.35% yr⁻¹ (VCU 1). The assessment of Brazilian cultivars released between 1998 and 2014 showed genetic gains in GY of 34.8 kg ha⁻¹ yr⁻¹ (1% yr⁻¹), demonstrating that the efforts of Brazilian research institutions to develop cultivars have produced additive results. The implications of genetic gain estimates on breeding programs are discussed.

OBJECTIVES To describe facial sinus anatomy from an endoscopic perspective and present a radiologic classification. METHODS Facial sinus was studied by endoscopy and high-resolution computed tomography (HRCT) scan in 39 temporal bones that underwent exclusive transcanal endoscopic approach. A radiomorphologic classification based on the relationship between the facial sinus and the mastoid portion of the facial nerve is created as follows. In type A facial sinus, the pneumatization of the facial sinus did not extend medially or posteriorly to the mastoid portion of the facial nerve. In type B facial sinus, the pneumatization extended posteriorly to the mastoid portion of the facial nerve. In type C facial sinus, the pneumatization extended posteriorly and medially to the mastoid portion of the facial nerve. RESULTS In all the specimens that underwent HRCT (n = 31), facial sinus could be identified, and its depth classified, in relation to the facial nerve. In this group, 58% type A, 29% type B, and 13% type C facial sinuses were identified. In all the specimens (n = 39), the facial sinus could be assessed by means of an exclusive endoscopic transcanal approach, and anatomical variants of the chordiculus, previously known as chordal ridge, could be described: ridge (39%), bridge (18%), incomplete (15%), and absent (28%). CONCLUSION Endoscopic exploration of the retrotympanum guarantees a very good exposure of the facial sinus, allowing detailed anatomic descriptions of its conformation and relationships with other structures. Improvement in our knowledge of its anatomy might decrease the possibility of residual disease during cholesteatoma surgery. Angled endoscopes (e.g. 45 °, 70 °) can guarantee a better view of the facial sinus. LEVEL OF EVIDENCE NA. Laryngoscope, 128:2397-2402, 2018.

BACKGROUND Pest control in post-harvest food storage represents a great challenge in the sustainable prevention of food losses, and insecticide-treated netting may represent a valid alternative to traditional practices such as direct application of insecticides. In our work, the efficacy of a permethrin-incorporated net, in combination with polypropylene or jute sacking, was tested, for the control of S. oryzae. Contamination of maize grain by permethrin from the treated netting was also evaluated. RESULTS A 98% control of S. oryzae was achieved using permethrin-treated netting. Both jute and polypropylene acted as additional barriers, thus increasing efficacy to 100%. However results also showed the contamination of maize kernel by permethrin released from the treated netting. The concentration of residues in maize kernels increased with increasing temperature; however the use of jute or polypropylene significantly reduced (by 87% to 97%) the concentration of residues transferred to maize kernels. CONCLUSIONS Permethrin treated netting provided a high level of efficacy in the post-harvest protection of maize. Several factors influenced permethrin residue concentrations in grains when treated nets are used. Therefore, solutions should be found to prevent contamination of food stored in the bags that are treated with insecticides.

Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin, and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward hexosamine biosynthesis pathway (HBP), which fuels aberrant glycosylation patterns that are extensively observed in cancer cells. HBP depends on nutrient availability to produce its end product UDP-GlcNAc, and for this reason is considered a metabolic sensor pathway. UDP-GlcNAc is the substrate used for the synthesis of major types of glycosylation, including O-GlcNAc and cell surface glycans. In general, the rate limiting enzyme of HBP, GFAT, is overexpressed in many cancer types that present EMT features as well as aberrant glycosylation. Moreover, altered levels of O-GlcNAcylation can modulate cell morphology and favor EMT. In this review, we summarize some of the current knowledge that correlates glucose metabolism, aberrant glycosylation and hyper O-GlcNAcylation supported by HBP that leads to EMT activation. Developmental Dynamics 247:481-491, 2018. © 2017 Wiley Periodicals, Inc.

In a 46, XY individual, the presence of the Y chromosome harboring the testis-determining factor (SRY) triggers testis determination and differentiation. In a 46, XX individual, the absence of SRY along with the activation of genes associated with the female pathway leads to ovarian development. The latter process has long been considered as a default pathway. However, recent studies have cast doubts on this dogma. Here, after a brief overview of the main steps of ovarian development, we focus on three genes WNT4, RSPO1 and FOXL2 that are essential for ovarian determination, differentiation and/or maintenance. Especial attention is paid to FOXL2 whose mutations are responsible for the blepharophimosis syndrome, often associated with female infertility, and for cancer. We highlight the cooperation of WNT4, RSPO1 and FOXL2 within a regulatory network and the need for further research to better understand their role in defining and maintaining ovarian identity.

OBJECTIVES To describe facial sinus anatomy from an endoscopic perspective and present a radiologic classification. METHODS Facial sinus was studied by endoscopy and high-resolution computed tomography (HRCT) scan in 39 temporal bones that underwent exclusive transcanal endoscopic approach. A radiomorphologic classification based on the relationship between the facial sinus and the mastoid portion of the facial nerve is created as follows. In type A facial sinus, the pneumatization of the facial sinus did not extend medially or posteriorly to the mastoid portion of the facial nerve. In type B facial sinus, the pneumatization extended posteriorly to the mastoid portion of the facial nerve. In type C facial sinus, the pneumatization extended posteriorly and medially to the mastoid portion of the facial nerve. RESULTS In all the specimens that underwent HRCT (n = 31), facial sinus could be identified, and its depth classified, in relation to the facial nerve. In this group, 58% type A, 29% type B, and 13% type C facial sinuses were identified. In all the specimens (n = 39), the facial sinus could be assessed by means of an exclusive endoscopic transcanal approach, and anatomical variants of the chordiculus, previously known as chordal ridge, could be described: ridge (39%), bridge (18%), incomplete (15%), and absent (28%). CONCLUSION Endoscopic exploration of the retrotympanum guarantees a very good exposure of the facial sinus, allowing detailed anatomic descriptions of its conformation and relationships with other structures. Improvement in our knowledge of its anatomy might decrease the possibility of residual disease during cholesteatoma surgery. Angled endoscopes (e.g. 45 °, 70 °) can guarantee a better view of the facial sinus. LEVEL OF EVIDENCE NA. Laryngoscope, 128:2397-2402, 2018.

Quantitative Structure - Activity Relationship (QSAR) models play a central role in medicinal chemistry, toxicology and computer-assisted molecular design, as well as a support for regulatory decisions and animal testing reduction. Thus, assessing their predictive ability becomes an essential step for any prospective application. Many metrics have been proposed to estimate the model predictive ability of QSARs, which have created confusion on how models should be evaluated and properly compared. Recently, we showed that the metric Q F 3 2 is particularly well-suited for comparing the external predictivity of different models developed on the same training dataset. However, when comparing models developed on different training data, this function becomes inadequate and only dispersion measures like the root-mean-square error (RMSE) should be used. The intent of this work is to provide clarity on the correct and incorrect uses of Q F 3 2 , discussing its behavior towards the training data distribution and illustrating some cases in which Q F 3 2 estimates may be misleading. Hereby, we encourage the usage of measures of dispersions when models trained on different datasets have to be compared and evaluated.

The objective of the present work was to compare the Reshaped Sequential Replacement (RSR) algorithm with other well-known variable selection techniques in the field of Quantitative Structure–Property Relationship (QSPR) modelling. RSR algorithm is based on a simple sequential replacement procedure with the addition of several ‘reshaping’ functions that aimed to (i) ensure a faster convergence upon optimal subsets of variables and (ii) reject models affected by chance correlation, overfitting and other pathologies. In particular, three reference variable selection methods were chosen for the comparison (stepwise forward selection, genetic algorithms and particle swarm optimization), aiming to identify benefits and drawbacks of RSR with respect to these methods. To this end, several QSPR datasets regarding different physical–chemical properties and characterized by different objects/variables ratios were used to build ordinary least squares models; in addition, some well-known (Y-scrambling) and more recent (R-based functions) statistical tools were used to analyse and compare the results. The study highlighted the good capability of RSR to find optimal subsets of variables in QSPR modelling, comparable or better than those found by the other reference variable selection methods. Moreover, RSR resulted to be faster than some of the analysed variable selection techniques, despite its extensive exploration of the variables space. Copyright © 2014 John Wiley & Sons, Ltd.