An Innovative Treatment Using Calcium Hydroxyapatite for Non-Surgical Facial Rejuvenation: The Vectorial-Lift Technique.

BACKGROUND: The facial aging process entails alterations in the volume, shape, and texture of all skin layers over time. Calcium hydroxyapatite (CaHA) is a well-established safe skin filler with unique properties to resolve some skin alterations by stimulating neocollagenesis. The vectoral-lift (V-lift) technique targets the global repositioning of facial structures by addressing distinct anatomical injection planes. It includes deep facial augmentation with Radiesse PlusTM to retain ligament restructuring and superficial subcutaneous enhancement with diluted Radiesse DuoTM. Herein, we present cases that illustrate the use of this approach. METHODS: This pilot study enrolled 36 participants (33 women and three men; ages 37-68 years) in a Brazilian clinical setting, and all patients underwent a single treatment. Photographs were taken at rest, in frontal and oblique views, before injection, and 90 days after treatment. RESULTS: Treatment resulted in elevation of the upper and middle face, notable improvements in the infraorbital hollow, and adjustment of the mean facial volume. CONCLUSIONS: The V-lift technique is a three-dimensional pan-facial treatment that relies on ligament support and face vectoring to obtain a lifting effect and facial contour restoration. It encompasses deep facial augmentation involving the use of Radiesse PlusTM for restructuring and retaining ligaments and Radiesse DuoTM for superficial subcutaneous enhancement. This approach targets a global repositioning of the facial structures by addressing distinct anatomical injection planes. It achieves a repositioning of the overall facial anatomy without requiring a substantial volumetric expansion. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Classification of Corrosion Severity in SPCC Steels Using Eddy Current Testing and Supervised Machine Learning Models.

Steel Plate Cold-Rolled Commercial (SPCC) steel is known to have long-term durability. However, it still undergoes corrosion when exposed to corrosive environments. This paper proposes an evaluation method for assessing the corrosion level of SPCC steel samples using eddy current testing (ECT), along with two different machine learning approaches. The objective is to classify the corrosion of the samples into two states: a less corroded state (state-1) and a highly corroded state (state-2). Generative and discriminative models were implemented for classification. The generative classifier was based on the Gaussian mixture model (GMM), while the discriminative model was based on the logistic regression model. The features used in the classification models are the peaks of the perturbated magnetic fields at two different frequencies. The performance of the classifiers was evaluated using metrics such as absolute error, accuracy, precision, recall, and F1 score. The results indicate that the GMM model is more conducive to categorizing states with higher levels of corrosion, while the logistic regression model is helpful in estimating states with lower levels of corrosion. Meanwhile, high classification accuracy can be achieved based on both methods using eddy current testing.

Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

Adhesive Porosity Analysis of Composite Adhesive Joints Using Ultrasonic Guided Waves.

Adhesively bonded composite joints can develop voids and porosity during fabrication, leading to stress concentration and a reduced load-carrying capacity. Hence, adhesive porosity analysis during the fabrication is crucial to ensure the required quality and reliability. Ultrasonic-guided wave (UGW)-based techniques without advanced signal processing often provide low-resolution imaging and can be ineffective for detecting small-size defects. This article proposes a damage imaging process for adhesive porosity analysis of bonded composite plates using UGWs measured by scanning laser Doppler vibrometer (LDV). To implement this approach, a piezoelectric transducer is mounted on the composite joint specimen to generate UGWs, which are measured over a densely sampled area. The signals obtained from the scan are processed using the proposed signal processing in different domains. Through the utilization of filter banks in frequency and wavenumber domains, along with the root-mean-square calculation of filtered signals, damage images of the adhesive region are obtained. It has been observed that different filters provide information related to different void sizes. Combining all the images reconstructed by filters, a final image is obtained which contains damages of various sizes. The images obtained by the proposed method are verified by radiography results and the porosity analysis is presented. The results indicate that the proposed methodology can detect the pores with the smallest detectable pore area of 2.41 mm2, corresponding to a radius of 0.88 mm, with an overall tendency to overestimate the pore size by an average of 11%.

Advanced Injection of Botulinum Toxin in the Nasal Muscles: A Novel Dynamic Change in Facial Expression.

BACKGROUND: Among the nasal muscles, the levator labii superior alaeque nasi (LLSAN) acts as a transitional muscle that conjugates with other nasal and perinasal muscles. Thus, when treating the nasal region with Botulinum toxin (BTX), it is important to understand local nasal muscular dynamics and how they can influence the muscular dynamics of the entire face. METHODS: This is a retrospective analysis of cases treated by an injection pattern encompassing the face, including nasal muscles. Photographs were taken at rest and during motion (frontal and oblique views), before and after treatment. RESULTS: A total of 227 patients have been treated in the last 18 months with the following results: eyebrow tail lifting, softness of crow's feet, improvement of the drooping of the tip of the nose, and shortening of the lip philtrum when smiling. We present cases illustrating the use of this approach. CONCLUSIONS: Treating the facial muscles globally (including the frontal, corrugators, procerus, orbicularis oculi, platysma, DAO, and nasal muscles) can improve the smile and facial expressions. This is believed to occur because the elevated portion of the upper lip muscle becomes stronger as the nasal part of the LLSAN is paralyzed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Baseline-Free Damage Imaging of Composite Lap Joint via Parallel Array of Piezoelectric Sensors.

This paper presents a baseline-free damage imaging technique using a parallel array of piezoelectric sensors and a control board that facilitates custom combinations of sensor selection. This technique incorporates an imaging algorithm that uses parallel beams for generation and reception of ultrasonic guided waves in a pitch-catch configuration. A baseline-free reconstruction algorithm for probabilistic inspection of defects (RAPID) algorithm is adopted. The proposed RAPID method replaces the conventional approach of using signal difference coefficients with the maximum signal envelope as a damage index, ensuring independence from baseline data. Additionally, conversely to the conventional RAPID algorithm which uses all possible sensor combinations, an innovative selection of combinations is proposed to mitigate attenuation effects. The proposed method is designed for the inspection of lap joints. Experimental measurements were carried out on a composite lap joint, which featured two dissimilar-sized disbonds positioned at the lap joint's borderline. A 2D correlation coefficient was used to quantitatively determine the similarity between the obtained images and a reference image with correct defect shapes and locations. The results demonstrate the effectiveness of the proposed damage imaging method in detecting both defects. Additionally, parametric studies were conducted to illustrate how various parameters influence the accuracy of the obtained imaging results.

A Shared Perspective on in Vitro and in Vivo Models to Assay Intestinal Transepithelial Transport of Food Compounds.

Assessing nutrient bioavailability is complex, as the process involves multiple digestion steps, several cellular environments, and regulatory-metabolic mechanisms. Several in vitro models of different physiological relevance are used to study nutrient absorption, providing significant challenges in data evaluation. However, such in vitro models are needed for mechanistic studies as well as to screen for biological functionality of the food structures designed. This collaborative work aims to put into perspective the wide-range of models to assay the permeability of food compounds considering the particular nature of the different molecules, and, where possible, in vivo data are provided for comparison.

From data to insight: Exploring contaminants in different food groups with literature mining and machine learning techniques.

Food remains a major source of human exposure to chemical contaminants that are unintentionally present in commodities globally, despite strict regulation. Scientific literature is a valuable source of quantification data on those contaminants in various foods, but manually summarizing the information is not practicable. In this review, literature mining and machine learning techniques were applied in 72 foods to obtain relevant information on 96 contaminants, including heavy metals, polychlorinated biphenyls, dioxins, furans, polycyclic aromatic hydrocarbons (PAHs), pesticides, mycotoxins, and heterocyclic aromatic amines (HAAs). The 11,723 data points collected from 254 papers from the last two decades were then used to identify the patterns of contaminants distribution. Considering contaminant categories, metals were the most studied globally, followed by PAHs, mycotoxins, pesticides, and HAAs. As for geographical region, the distribution was uneven, with Europe and Asia having the highest number of studies, followed by North and South America, Africa and Oceania. Regarding food groups, all contained metals, while PAHs were found in seven out of 12 groups. Mycotoxins were found in six groups, and pesticides in almost all except meat, eggs, and vegetable oils. HAAs appeared in only three food groups, with fish and seafood reporting the highest levels. The median concentrations of contaminants varied across food groups, with citrinin having the highest median value. The information gathered is highly relevant to explore, establish connections, and identify patterns between diverse datasets, aiming at a comprehensive view of food contamination.

Locating and Imaging Fiber Breaks in CFRP Using Guided Wave Tomography and Eddy Current Testing.

In this paper, guided Lamb wave tomography and eddy current testing (ECT) techniques were combined to locate and evaluate fiber breaks in carbon-fiber-reinforced plastic (CFRP) structures. Guided wave testing (GWT) and computed tomography (CT) imaging were employed to quickly locate fiber breaks in the CFRP plate. From B-scans performed along two different fiber orientations (0 and 90 degrees), parallel-beam projections of different features were extracted from the guided wave signals, using signal-processing techniques (such as wavelet and Hilbert transforms) and statistical functions (such as skewness and kurtosis). The parallel-beam projections of each individual feature were used as input in computed tomography imaging reconstruction to approximately estimate the location of fiber breaks. From the obtained reconstructed images, image-fusion techniques were applied to get complementary information from multiple source images into one single image. After locating the fiber breaks, C-scans were performed in the vicinity of the damage, using an ECT probe with double excitation configuration to evaluate the condition of the fiber break.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

Experimental Estimation of Lamb Wave Dispersion Curves for Adhesively Bonded Aluminum Plates, Using Two Adjacent Signals.

In this study, dispersion curve estimation of a bonded aluminum plate is carried out by proposing a specific signal processing procedure. In this proposed method, the angle beam ultrasonic transducer measurement system in a pitch-catch configuration is used to acquire Lamb wave signals from two adjacent positions. The obtained signals are processed then by using signal processing techniques, including bandpass filters, fast Fourier transform (FFT), and bandpass Gaussian filters. Various transmitted signals with different central frequencies are used to estimate four modes of the utilized bonded specimen for frequencies less than 1 MHz. The dispersion curve results in terms of phase velocity and wavenumbers are compared with theoretical dispersion curves and 2-D FFT. This comparison is carried out by using three different metrics, which shows the maximum mean relative error of 3.46% with low variance.

Noncanonical roles of p53 in cancer stemness and their implications in sarcomas.

Impairment of the prominent tumor suppressor p53, well known for its canonical role as the "guardian of the genome", is found in almost half of human cancers. More recently, p53 has been suggested to be a crucial regulator of stemness, orchestrating the differentiation of embryonal and adult stem cells, suppressing reprogramming into induced pluripotent stem cells, or inhibiting cancer stemness (i.e., cancer stem cells, CSCs), which underlies the development of therapy-resistant tumors. This review addresses these noncanonical roles of p53 and their implications in sarcoma initiation and progression. Indeed, dysregulation of p53 family proteins is a common event in sarcomas and is associated with poor survival. Additionally, emerging studies have demonstrated that loss of wild-type p53 activity hinders the terminal differentiation of mesenchymal stem cells and leads to the development of aggressive sarcomas. This review summarizes recent findings on the roles of aberrant p53 in sarcoma development and stemness and further describes therapeutic approaches to restore normal p53 activity as a promising anti-CSC strategy to treat refractory sarcomas.

Structural and Drug Targeting Insights on Mutant p53.

p53 is a transcription factor with a pivotal role in cell homeostasis and fate. Its impairment is a major event in tumor onset and development. In fact, about half of human cancers bear TP53 mutations that not only halt the normal function of p53, but also may acquire oncogenic gain of functions that favor tumorigenesis. Although considered undruggable for a long time, evidence has proven the capability of many compounds to restore a wild-type (wt)-like function to mutant p53 (mutp53). However, they have not reached the clinic to date. Structural studies have strongly contributed to the knowledge about p53 structure, stability, dynamics, function, and regulation. Importantly, they have afforded relevant insights into wt and mutp53 pharmacology at molecular levels, fostering the design and development of p53-targeted anticancer therapies. Herein, we provide an integrated view of mutp53 regulation, particularly focusing on mutp53 structural traits and on targeting agents capable of its reactivation, including their biological, biochemical and biophysical features. With this, we expect to pave the way for the development of improved small molecules that may advance precision cancer therapy by targeting p53.

A Diarylpentanoid with Potential Activation of the p53 Pathway: Combination of in silico Screening Studies, Synthesis, and Biological Activity Evaluation.

In silico studies of a library of diarylpentanoids led us to the identification of potential new MDM2/X ligands. The diarylpentanoids with the best docking scores obeying the druglikeness and ADMET prediction properties were subsequently synthesized and evaluated for their antiproliferative activity on colon cancer HCT116 and fibroblasts HFF-1 cells. The effect on p53-MDM2/X interactions was evaluated through yeast-based assays for compounds showing potent antiproliferative activity in HCT116 cells and low toxicity in normal cells, resulting in the identification of a potential dual inhibitor. Moreover, its antiproliferative effect was significantly reduced in the absence of p53 and in MDA-MB-231 cells expressing a mutant p53 form. The antiproliferative effect of this compound was associated with induction of cell cycle arrest, apoptosis, PARP cleavage and increased p53 and its transcriptional targets, p21 and PUMA, in HCT116 cells. Docking poses and residues involved in the inhibition of p53-MDM2/X interactions were predicted by docking studies.

A selective p53 activator and anticancer agent to improve colorectal cancer therapy.

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.

Management of Patients Seeking Surgical Rhinoplasty with Previous Nasal Injections of Hyaluronic Acid.

BACKGROUND: Patients are looking for procedures which are minimally invasive and consequently incur minimal downtime. However, these procedures are not usually long lasting and have limited outcomes both esthetically and functionally. For these reasons, the number of patients seeking surgical rhinoplasty and who have previous nasally injected hyaluronic acid is increasing. METHODS: The aim of this article is to provide the surgeon with information for both the identification and surgical approach for those patients who seek nasal cosmetic surgery, and who have previously been treated with nasal injections of hyaluronic acid filler. RESULTS: We present cases that illustrate the use of this approach and suggest three possible patient management. CONCLUSIONS: There are three possible approaches: wait HA to be naturally reabsorbed; apply hyaluronidase before the surgery or proceed to rhinoplasty with no prior application of hyaluronidase. The physician must be aware of this progression and know how to manage each case to optimize the surgical outcome. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Outcome of Free Diced Cartilage Grafts in Rhinoplasty: A Systematic Review.

Diced cartilage grafts are used to increase and refine the nasal contour, providing easy molding and versatility when compared with block grafts. However, all grafts present the possibility of visibility, distortion, and absorption. The aim of this study is to evaluate, through a systematic review, the outcome of the use of the free diced graft cartilage in rhinoplasty. A systematic search of the literature was performed in the databases (PubMed, Lilacs, Scielo, Cochrane) with the terms "diced cartilage" and "rhinoplasty." Studies were selected according to the inclusion and exclusion criteria and data extracted and grouped for analysis. Six eligible studies were included. In total, 4,044 patients underwent rhinoplasty with free diced cartilage graft, with 61 (1.51%) of them requiring reoperation. The main reasons were overcorrection and irregularities of the nasal dorsum. The infection rate was reported in three studies, with 2 (0.06%) of 3,252 patients presenting infection at the graft site. Two cases of displacement were treated with external molding, without reoperation. The graft resorption was reported in four articles, which described 22 (0.67%) cases of partial resorption in 3,288 patients. Therefore, the available evidence suggests that resorption of the graft and unfavorable outcomes are rare.

The success of particular Acinetobacter baumannii clones: accumulating resistance and virulence inside a sugary shield.

BACKGROUND: In Portugal, carbapenem-resistant Acinetobacter baumannii (CRAB) has been associated with ST98, ST103 and ST208 (Oxford Scheme, Oxf) and a clone has usually been associated with a particular period of time. These clonal shifts were primarily explained by an increased antimicrobial resistance profile. Here we explore genomic and biochemical differences among these and more recent clones, which could further explain the diversity and evolution of this species. METHODS: A total of 116 CRAB isolates (2010-15), together with representatives of a previously described CRAB collection (4 isolates, 2001-06) were characterized by attenuated total reflection Fourier transform infrared spectroscopy (FTIR-ATR) and MLST. Representatives of different FTIR-ATR/MLST clusters were selected for WGS (n = 13), which allowed the in silico extraction of resistance and virulence genes, capsule locus and SNP analysis. RESULTS: A. baumannii clonal shifts of OXA-58-producing ST103Oxf (2001-04), OXA-40-producing ST98Oxf (2002-06), OXA-23-producing ST208Oxf (2006-10) and OXA-23-producing ST218Oxf (2010-15) were accompanied by an increase in AMR genes and virulence factors. FTIR-ATR clustering was congruent with sugar composition predicted from the capsular locus: a fucosamine cluster comprising ST98Oxf, ST103Oxf and a single ST218Oxf isolate; a pseudaminic acid cluster of ST208Oxf and ST1557Oxf isolates; and legionaminic acid, resembling the sialic acid from mammalian cells, in a cluster comprising ST218Oxf isolates. The whole-genome phylogenetic tree was congruent with MLST, with isolates presenting 5-28 938 SNPs. ST208Oxf and ST218Oxf presented ∼1900 SNPs while ST103Oxf and ST1557Oxf showed a greater number of SNPs (∼28 000). CONCLUSIONS: Clonal shifts of CRAB were promoted, in our country, by consecutive virulence and AMR gene pool enlargement, together with features increasing pathogen-host adaptation. Worldwide dominance of ST218Oxf is supported by the combination of high AMR and virulence levels.

Machine Learning Photovoltaic String Analyzer.

Photovoltaic (PV) system energy production is non-linear because it is influenced by the random nature of weather conditions. The use of machine learning techniques to model the PV system energy production is recommended since there is no known way to deal well with non-linear data. In order to detect PV system faults, the machine learning models should provide accurate outputs. The aim of this work is to accurately predict the DC energy of six PV strings of a utility-scale PV system and to accurately detect PV string faults by benchmarking the results of four machine learning methodologies known to improve the accuracy of the machine learning models, such as the data mining methodology, machine learning technique benchmarking methodology, hybrid methodology, and the ensemble methodology. A new hybrid methodology is proposed in this work which combines the use of a fuzzy system and the use of a machine learning system containing five different trained machine learning models, such as the regression tree, artificial neural networks, multi-gene genetic programming, Gaussian process, and support vector machines for regression. The results showed that the hybrid methodology provided the most accurate machine learning predictions of the PV string DC energy, and consequently the PV string fault detection is successful.