Impact of enhancement filters of a CMOS system on halo artifact expression at the bone-to-implant interface.

OBJECTIVE: To assess the impact of enhancement filters on the formation of halo artifacts in radiographs of dental implants obtained with a complementary metal oxide semiconductor (CMOS) system. METHODS: Digital radiographs of dental implants placed in dry human mandibles were processed with the Noise Reduction smoothing filter, as well as the Sharpen 1, Sharpen 4, and Sharpen UM high-pass filters available in the CLINIVIEW™ software (Instrumentarium Dental, Tuusula, Finland). Subjective analysis involved evaluating the left, right, and apical surfaces of each implant for the presence of much, few, or no halo. The objective analysis involved measurement of the halo area using the Trainable Weka Segmentation plugin (ImageJ, National Institutes of Health, Bethesda, MD, USA). Data were analyzed using Friedman's test (subjective analysis) and ANOVA (objective analysis) (α = 5%). RESULTS: In the subjective evaluation, the Sharpen 4 filter produced more radiographs with much halo present, and in the objective evaluation, a bigger halo area when compared to the original images and the Noise Reduction filter for all surfaces (p < 0.05). CONCLUSIONS: When evaluating dental implants, priority should be given to original images and those enhanced with smoothing filters since they exhibit fewer halo artifacts. CLINICAL RELEVANCE: Post-processing tools, such as enhancement filters, may improve the image quality and assist some diagnostic tasks. However, little is known regarding the impact of enhancement filters in halo formation on CMOS systems, which have been increasingly used in dental offices.

CHEK2 germline variants identified in familial nonmedullary thyroid cancer lead to impaired protein structure and function.

Approximately 5 to 15% of nonmedullary thyroid cancers (NMTC) present in a familial form (familial nonmedullary thyroid cancers [FNMTC]). The genetic basis of FNMTC remains largely unknown, representing a limitation for diagnostic and clinical management. Recently, germline mutations in DNA repair-related genes have been described in cases with thyroid cancer (TC), suggesting a role in FNMTC etiology. Here, two FNMTC families were studied, each with two members affected with TC. Ninety-four hereditary cancer predisposition genes were analyzed through next-generation sequencing, revealing two germline CHEK2 missense variants (c.962A > C, p.E321A and c.470T > C, p.I157T), which segregated with TC in each FNMTC family. p.E321A, located in the CHK2 protein kinase domain, is a rare variant, previously unreported in the literature. Conversely, p.I157T, located in CHK2 forkhead-associated domain, has been extensively described, having conflicting interpretations of pathogenicity. CHK2 proteins (WT and variants) were characterized using biophysical methods, molecular dynamics simulations, and immunohistochemistry. Overall, biophysical characterization of these CHK2 variants showed that they have compromised structural and conformational stability and impaired kinase activity, compared to the WT protein. CHK2 appears to aggregate into amyloid-like fibrils in vitro, which opens future perspectives toward positioning CHK2 in cancer pathophysiology. CHK2 variants exhibited higher propensity for this conformational change, also displaying higher expression in thyroid tumors. The present findings support the utility of complementary biophysical and in silico approaches toward understanding the impact of genetic variants in protein structure and function, improving the current knowledge on CHEK2 variants' role in FNMTC genetic basis, with prospective clinical translation.

Influence of notebook computers screens and undergraduate level of dental students in the radiographic detection of carious lesions

Aim: To evaluate the influence of notebook computers screens and undergraduate level of dental students in the radiographic detection of carious lesions. Methods: Bitewing digital radiographs were presented to 3rd and 5th year dental students in three different notebooks computers: Notebook 1 with anti-glare screen (1366×768 pixels), Notebook 2 without anti-glare screen (1366×768 pixels), and Notebook 3 with anti-glare screen (1920×1080 pixels). A reference standard based on a consensus analysis was set by three senior professors of Oral Radiology and Cariology. Sensitivity, specificity and accuracy values were measured and submitted to two-way ANOVA at a significance level of 5%. Results: Notebook 2 provided significantly lower sensitivity values (Mean 56.5% ± 2.94) than notebook 3 (71.1% ± 2.82) (p = 0.002). We found no statistically significant differences between the two undergraduate years (p > 0.05). Conclusion: The anti-glare screen of notebook computers screens can influence the radiographic detection of carious lesions, but the undergraduate level of dental students does not influence this diagnostic task

Effect of Dietary Incorporation of Yellow Mealworm as a Partial Fishmeal Replacer on Growth, Metabolism, and Intestinal Histomorphology in Juvenile Meagre (Argyrosomus regius).

Efforts have been made to find alternatives to fish meal (FM), as the sustainability of aquaculture depends on it. Insect meal (IM) is a potential candidate to partially replace FM, being more sustainable and economically viable. In this experimental trial, three diets were tested with different yellow mealworm incorporation: a control diet with no IM, a diet with an inclusion of 10% IM (Ins10), and a diet with an incorporation of 20% IM (Ins20). The diets were tested on 10.5 g meagre for 47 days. The results showed that an IM inclusion higher than 10% affected both growth (2.6 vs. 2.2) and FCR (1.5 vs. 1.9) of meagre juveniles. However, this reduction in growth did not result from lower protein retention or changes in muscle fibre area or density. Little differences were observed in the activity of pancreatic and intestinal enzymes except for aminopeptidase total activity which was higher in the control and Ins10 compared to Ins20 (3847 vs. 3540 mU/mg protein), suggesting no limitations in protein synthesis. Also, the alkaline phosphatase intestinal maturation index was higher in the control group compared to the IM groups (437 vs. 296). On the contrary, several differences were also found in the proteolytic activity in the hepatic and muscle tissues of meagre juveniles fed the Ins10 diet. The inclusion of IM had no impact on intestine histomorphology but changes were detected in the enterocytes of fish from control and Ins10 which showed hypervacuolization and nucleus misplacement compared to the Ins20 treatment. Nevertheless, a higher percentage of Vibrionaceae was recorded for meagre fed on the Ins20 diet. Since no signs of inflammation were observed in the distal intestine, this suggests IM incorporation could have had an important impact on intestinal health due to its antimicrobial properties. This is supported by an increase in the haematocrit in the treatments where IM was added (20 to 25%). In conclusion, incorporations of IM at percentages up to 10% do not seem to have a negative impact on meagre performance at this age but can enhance the fish immune system and protection against intestinal inflammation.

DNA aneuploidy identifies a subset of Luminal subtype breast carcinoma patients with worse clinical outcome.

AIM: In breast carcinoma (BC), the relationship between the ploidy pattern and molecular subtyping is still unknown. We aim to investigate the prognostic impact of DNA ploidy within molecular subtypes of a large cohort of BC patients. METHODS: The series involved 520 BC patients with no neoadjuvant therapy and a median follow-up of 115.5 months. Immunohistochemical assessment of hormonal receptors, ERBB2 (HER2) status and Ki67 proliferative activity was the basis of the surrogate molecular subtyping. Ploidy was evaluated by DNA flow cytometry in fresh/frozen tumour samples. Kaplan-Meier (K-M) survival estimation was used for prognostic statistical analysis. RESULTS: Luminal A subtype had the lowest prevalence of disease recurrences (23.6 %) and deaths from disease (18.3 %), while Luminal B (42.2 %/37.9 %), Triple-negative (46.4 %/40.6 %), and HER2-positive (55.9 %/50.0 %) subtypes had the highest. The Triple-positive subtype shows an intermediate/low frequency of adverse events (29.4 % of disease recurrences and 17.6 % of deaths from disease). Luminal A tumours were mostly diploid (55.3 %), while Triple-negative and HER2-positive tumours showed a high incidence of aneuploidy (82.6 % and 88.2 %, respectively). Luminal B and Triple-positive tumours had an intermediate percentage of aneuploidy (63.8 % and 70.6 %, respectively). K-M survival curves showed that DNA aneuploidy is significantly associated with shorter disease-free survival and overall survival in Luminal A and Luminal B molecular subtypes. CONCLUSION: DNA aneuploidy identifies a subset of Luminal BC patients with worse clinical outcome, potentially eligible for more aggressive adjuvant therapy.

Collagenous sprue: a rare cause of watery diarrhea and villous atrophy - case report.

Collagenous sprue is a rare and unrecognized cause of diarrhea and weight loss, mainly affecting the duodenum and small bowel. The clinical picture often resembles that of coeliac sprue, the main differential diagnosis, albeit, being refractory to a gluten-free diet. The histological features are fundamentally characterized by the deposition of collagen beneath the basement membrane of gut mucosa. Treatment should be initiated as soon as the diagnosis is established, so as to prevent the progression of fibrosis. We will describe the case of a 76-year-old woman with collagenous sprue, her diagnostic workup, histopathological examination, and response to treatment.

Biometric Recognition: A Systematic Review on Electrocardiogram Data Acquisition Methods.

In the last decades, researchers have shown the potential of using Electrocardiogram (ECG) as a biometric trait due to its uniqueness and hidden nature. However, despite the great number of approaches found in the literature, no agreement exists on the most appropriate methodology. This paper presents a systematic review of data acquisition methods, aiming to understand the impact of some variables from the data acquisition protocol of an ECG signal in the biometric identification process. We searched for papers on the subject using Scopus, defining several keywords and restrictions, and found a total of 121 papers. Data acquisition hardware and methods vary widely throughout the literature. We reviewed the intrusiveness of acquisitions, the number of leads used, and the duration of acquisitions. Moreover, by analyzing the literature, we can conclude that the preferable solutions include: (1) the use of off-the-person acquisitions as they bring ECG biometrics closer to viable, unconstrained applications; (2) the use of a one-lead setup; and (3) short-term acquisitions as they required fewer numbers of contact points, making the data acquisition of benefit to user acceptance and allow faster acquisitions, resulting in a user-friendly biometric system. Thus, this paper reviews data acquisition methods, summarizes multiple perspectives, and highlights existing challenges and problems. In contrast, most reviews on ECG-based biometrics focus on feature extraction and classification methods.

Malignant Hypercalcemia Due to the Ectopic Production of Calcitriol by an Abdominal Liposarcoma.

Hypercalcemia of malignancy (HM) is a common form of paraneoplastic syndrome associated with a poor prognosis of the disease. In solid tumors, HM occurs mainly due to the production of parathyroid hormone-related peptide (PTHrP). We present a case of a 60-year-old male with a 25 cm retroperitoneal liposarcoma diagnosed with severe hypercalcemia (16.8 mg/dL) by a preoperative blood sampling. Hypercalcemia workup showed suppressed parathyroid hormone (PTH), normal PTHrP, and high 1,25-dihydroxyvitamin D (1,25(OH)2D) serum levels. After surgery, hypercalcemia and calcitriol levels normalized. Immunohistochemical analysis of the tumor showed 1α-hydroxylase expression by tumor cells. To our knowledge, this is the first case of liposarcoma-associated hypercalcemia caused exclusively by the ectopic production of calcitriol. Despite being a rare cause of hypercalcemia, measuring 1,25(OH)2D should be considered in the workup of a patient with high serum calcium levels, suppressed PTH, and normal PTHrP.

Medulloblastoma Development in a Patient with a Constitutional Balanced t(5;22)(q35.1;q11.2) Involving the NF2 Gene.

Neurofibromatosis type 2 (NF2) is a brain tumor predisposing syndrome caused by inactivating alterations of the NF2 gene mapped at chromosome 22q. Currently, no genetic information exists on medulloblastomas occurring in NF2 patients. We herein report on the genetic alterations observed in a girl in which the NF2 gene was de novo altered due to a constitutional translocation: t(5;22)(q35.1;q11.2). This girl had a particularly aggressive disease course. At the age of 4, she had already been diagnosed with three lesions classified as schwannomas and a meningioma. At 10 years old, she developed a medulloblastoma. She died at the age of 14 due to a refractory acute myeloid leukemia (AML). From the genetic point of view, we observed that (1) the NF2 gene was rearranged in all patient samples: blood, tumor, and leukemic cells; (2) loss of 3' region of NF2 and the downstream regions of chromosome 22 were only detected in medulloblastoma cells; (3) the known cancer AML-related gene: NPM1 which is mapped at 5q35.1 was not the target of any alteration in our patient. Our data suggest that inactivation of the NF2 gene was relevant for the medulloblastoma pathogenesis. Furthermore, we know that malignant cancers are the result of a multi-epi-genetic sequence of events, and although, unquestionably limited to the genetic findings in one case. We may hypothesize, that as described for a fraction of medulloblastomas, the alteration of a gene mapped at 5q might also have been relevant for medulloblastoma development in our patient.

Plant-based diets fed to juvenile meagre Argyrosomus regius with low methionine and taurine supplementation led to an overall reduction in fish performance and to an increase in muscle fibre recruitment.

Methionine and taurine are amino acids (AA) that are usually deficient when fish meal is replaced by plant proteins. In this study, three diets were tested in juvenile meagre (initial weight: 13.4 g) for 8 weeks. The D1 diet had 0.2% methionine and 1% taurine supplementation; the D2 and D3 diets had 0.6% methionine and 1% and 2% taurine supplementation, respectively. The results showed that meagre fed the D1 diet had lower specific growth rate (2.2 to 2.5), lower feed efficiency (0.9 to 1.2) and higher food conversion rate (FCR, 1.1 to 0.8) as well as a lower activity of the alanine aminotransferase (ALAT) enzyme. Furthermore, a higher recruitment of muscle fibres (46% compared to 36%) as well as a higher fibre density was observed (1019 compared to 870 fibres mm-2 ). This study shows that meagre requires a sufficient quantity of methionine in plant-based diets to avoid a reduction in fish performance. Furthermore, taurine supplementation in the D1 diet was not able to mitigate the effects of methionine deficiency. A higher taurine supplementation did not improve meagre performance.

S-phase fraction, lymph node status and disease staging as the main prognostic factors to differentiate between young and older patients with invasive breast carcinoma.

The influence of age on the outcome of patients with invasive breast carcinoma (IBC) has not yet been fully established. The present study investigated two subgroups of patients either side of the age spectrum, and evaluated cytometric, histopathological and molecular characteristics. The series involved 219 patients with IBC that had long-term follow-up, which were divided into two subgroups: Young (≤45 years; n=103) and old patients (≥75 years; n=116). Immunohistochemical evaluation of hormonal receptors, Ki67 index and HER2 status (plus HER2 silver in situ hybridization in equivocal cases) were used as the basis for surrogate molecular subtyping. Ploidy and S-phase fraction (SPF) were analysed by DNA flow cytometry. Differences between the subgroups' characteristics were assessed by the two proportion Z test. Kaplan-Meier estimation and log-rank test were applied for survival analyses. The median age in the subgroups were 40 years (range, 19-45 years) in the young group and 78 years (range, 75-91 years) in the older subgroup. Young patients exhibited higher lymph node involvement, more advanced disease staging, higher SPF tumour proliferative activity, and a trend of lower incidence of Luminal A and higher incidence of Luminal B tumours. The median SPF value was significantly higher in young patients [7.1% (range, 1.5-23.7%) vs. 4.5% (range, 0.7-26.4%)], whereas the ploidy pattern showed no significant difference. In the whole series, as within IBC of no special type, young patients had a higher rate of recurrence (46.6 vs. 22.4%; P<0.001) and deaths from disease (35.9 vs. 20.7%; P=0.030), with a statistically significant difference for disease-free survival. In conclusion, the present study indicated that young patients with IBC exhibited more aggressive disease, with an increased risk of recurrence and shorter disease-free survival. SPF, lymph node status and staging appeared to be the main prognostic factors to differentiate young from older patients with IBC.

Initial Study Using Electrocardiogram for Authentication and Identification.

Recently, several studies have demonstrated the potential of electrocardiogram (ECG) to be used as a physiological signature for biometric systems (BS). We investigated the potential of ECG as a biometric trait for the identification and authentication of individuals. We used data from a public database, CYBHi, containing two off-the-person records from 63 subjects, separated by 3 months. For the BS, two templates were generated: (1) cardiac cycles (CC) and (2) scalograms. The identification with CC was performed with LDA, kNN, DT, and SVM, whereas a convolutional neural network (CNN) and a distance-based algorithm were used for scalograms. The authentication was performed with a distance-based algorithm, with a leave-one-out cross validation, for impostors evaluation. The identification system yielded accuracies of 79.37% and 69.84% for CC with LDA and scalograms with CNN, respectively. The authentication yielded an accuracy of 90.48% and an impostor score of 13.06% for CC, and it had an accuracy of 98.42% and an impostor score of 14.34% for scalograms. The obtained results support the claim that ECG can be successfully used for personal recognition. To the best of our knowledge, our study is the first to thoroughly compare templates and methodologies to optimize the performance of an ECG-based biometric system.

HIF-1α inhibitor PX-478 preserves pancreatic ß cell function in diabetes.

During progression of type 2 diabetes, pancreatic ß cells are subjected to sustained metabolic overload. We postulated that this state mediates a hypoxic phenotype driven by hypoxia-inducible factor-1α (HIF-1α) and that treatment with the HIF-1α inhibitor PX-478 would improve ß cell function. Our studies showed that the HIF-1α protein was present in pancreatic ß cells of diabetic mouse models. In mouse islets with high glucose metabolism, the emergence of intracellular Ca2+ oscillations at low glucose concentration and the abnormally high basal release of insulin were suppressed by treatment with the HIF-1α inhibitor PX-478, indicating improvement of ß cell function. Treatment of db/db mice with PX-478 prevented the rise of glycemia and diabetes progression by maintenance of elevated plasma insulin concentration. In streptozotocin-induced diabetic mice, PX-478 improved the recovery of glucose homeostasis. Islets isolated from these mice showed hallmarks of improved ß cell function including elevation of insulin content, increased expression of genes involved in ß cell function and maturity, inhibition of dedifferentiation markers, and formation of mature insulin granules. In response to PX-478 treatment, human islet organoids chronically exposed to high glucose presented improved stimulation index of glucose-induced insulin secretion. These results suggest that the HIF-1α inhibitor PX-478 has the potential to act as an antidiabetic therapeutic agent that preserves ß cell function under metabolic overload.

Gestational diabetes in twin pregnancy: A predictor of adverse fetomaternal outcomes?

AIM: To compare fetomaternal outcomes between GDM pregnant women with twin versus singleton pregnancies and then between women with GDM versus non-GDM twin pregnancies. METHODS: We performed a retrospective study including GDM pregnant women with both twin and singleton pregnancies followed in our tertiary center between 2011 and 2018. The fetomaternal characteristics of each group were compared. We then compared women with GDM twin pregnancy followed at our institution between 2011 and 2018 to non-GDM twin pregnant women giving childbirth in 2018. RESULTS: A total of 1127 GDM pregnant women were evaluated: 42 with twin pregnancy and 1085 with singleton pregnancy. Preeclampsia (14.3% vs. 3.3%, p < 0.001) and cesarean delivery (76.2% vs. 36.9%, p < 0.001) were more frequent among women with twin pregnancy. Neonatal morbidity was also more common among neonates delivered from twin pregnant women, including preterm labor (73.8% vs. 7.8%, p < 0.001), hypoglycemia (6% vs. 4.8%, p = 0.043), hyperbilirubinemia (33.3% vs. 9.0%, p < 0.001), RDS (28.6% vs. 2.7%, p < 0.001), admission in NICU (32.1% vs. 4.5%, p < 0.001) and SGA (19.0% vs. 11.0%, p = 0.001). Overall there were no significant differences in fetomaternal morbidity parameters between GDM (n = 42) versus non-GDM (n = 83) twin pregnancies, although SGA infants were more frequent in the latter group (33.9% vs. 19.0%, p = 0.014). CONCLUSIONS: In GDM pregnant women, twin pregnancy seems to be associated with an increased prevalence of neonatal morbidity when compared to singleton pregnancy. On the other hand, in twin pregnancy, diagnosis of GDM does not seem to be associated with poorer fetomaternal outcomes. GDM seems to be protective for the occurrence of SGA neonates in twin pregnancies.

Influence of psoriasis lesions' location and severity on psychosocial disability and psychopathology. Observational study and psychometric validation of the SAPASI Portuguese version.

OBJECTIVES: The psychosocial impact of psoriasis is well documented. However, the contributing role of clinical disease characteristics is not satisfactorily explored. This study aimed to validate the Self-administered Psoriasis Area and Severity Index (SAPASI) to a Portuguese population (SAPASI-PT) and to perform its cross-validation, assessing how the results will generalize to an independent data set, with the Psoriasis Area and Severity Index (PASI), in order to assess the influence of psoriasis' severity on psychosocial disability and psychopathology. METHODS: A cross-sectional study with 228 patients with psoriasis was carried out. Data was collected through a sociodemographic and clinical questionnaire, SAPASI-PT, the Psoriasis Disability Index (PDI) and the Brief Symptoms Inventory (BSI). The cultural and linguistic adaptation of SAPASI to a Portuguese version and the cross validation with PASI was carried out. Multiple associations between psychosocial disability, psychopathology and severity, discomfort and location of lesions were investigated through logistic regression models. RESULTS: A good adjustment model for SAPASI-PT is found. Also, associations between psychosocial disability, psychopathology and the psoriasis severity and discomfort are found. The existence of lesions is positively associated with the severity of the disease. Patients with lesions in hands or genitals are those reporting a greater discomfort. The presence of lesions in hands is positively associated with PDI, i.e., with leisure and with treatment, marginally. Additionally, patients scoring higher in the personal dimension are found to have a significantly greater percentage of lesions in the genitals. CONCLUSIONS: The psoriasis severity and location of lesions are important determinants of patients´ quality of life. Lesions on face, hands and genitals are associated with a higher impact on psychosocial wellbeing of patients. Psychological counselling should be considered within psoriasis treatment context in patients with the described disease manifestations.

Positive Youth Development in the Context of Climate Change: A Systematic Review.

Climate change has been acknowledged as one of the most significant current threats for younger generations. However, few studies have focused on climate change impacts on youth and how they can be supported. The purpose of this systematic review is to emphasize that a developmental perspective is fundamental within the interdisciplinary studies concerning climate change. Specifically, we focus our research on how the Positive Youth Development framework may inform future approaches to promote adolescents' and young adults' well-being and engagement in the context of climate change. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search comprised two databases, and a total of 13 articles were finally considered eligible for review. Data were analyzed using a narrative method. The results show that the Positive Youth Development theory is not yet directly embedded in existing studies concerning adolescents and young adults in the context of climate change, but some of its principles were identified. Examples are provided of how Positive Youth Development characteristics and constructs can enhance future research, practice, and policies. We highlight this framework as an innovative and promising approach in the context of climate change.

Dehydropeptide Supramolecular Hydrogels and Nanostructures as Potential Peptidomimetic Biomedical Materials.

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, ß-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,ß-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.