Simulation of daily soft multifocal contact lenses using SimVis Gekko: from in-vitro and computational characterization to clinical validation.

Multifocal contact lenses (MCLs) are one of the solutions to correct presbyopia, but their adoption is not widespread. To address this situation, visual simulators can be used to refine the adaptation process. This study aims to obtain accurate simulations for a visual simulator (SimVis Gekko; 2EyesVision) of daily soft MCL designs from four manufacturers. In-vitro characterization of these MCLs-several powers and additions- was obtained using NIMO TR-1504. From the averaged relative power profiles across powers, phase maps were reconstructed and the Through-Focus Visual Strehl metric was calculated for each MCL design. The SimVis Gekko simulation corresponding to each MCL design was obtained computationally and bench-validated. Finally, the MCL simulations were clinically validated involving presbyopic patients. The clinical validation results show a good agreement between the SimVis Gekko simulations and the real MCLs for through-focus visual acuity (TF-VA) curves and VA at three real distances. All MCL designs showed a partial correlation higher than 0.90 and a Root Mean Square Error below 0.07 logMAR between the TF-VA of simulations and Real MCLs across subjects. The validity of the simulation approach using SimVis Gekko and in-vitro measurements was confirmed in this study, opening the possibility to accelerate the adaptation of MCLs.

Improving outcomes for patients with hard-to-heal wounds following adoption of the Wound Hygiene Protocol: real-world evidence.

OBJECTIVE: To evaluate the impact of a four-step biofilm-based wound care strategy, Wound Hygiene Protocol (WHP: cleanse, debride, refashion, and dress), on hard-to-heal wounds. METHOD: This was a prospective, real-world analysis of hard-to-heal wounds managed with the WHP that incorporated Aquacel Ag+ (Convatec Ltd., UK) dressings. Data were captured electronically between April 2021 and December 2022. The primary endpoint was change in wound volume from baseline to final assessment. RESULTS: A total of 693 wounds in 669 patients (median patient age: 74 years) were included in the analysis with a median treatment time of 31 days. Most health professionals were general nurses (50%) or nurse practitioners (38%). Patient homes (27%) and community clinics (27%) were the most common clinical settings. Venous leg ulcers (26%) and pressure ulcers/injuries (17%) were the most common wound type. Duration was >12 months in 21% of wounds. At baseline, the mean wound volume was 57.8cm3. At the final assessment, mean wound volume was 17.2cm3, corresponding to an 80% reduction from baseline; p<0.001). At baseline, 66% of wounds were static or deteriorating. At final assessment, this had decreased to 5%, and 94% had improved or healed. Exudate levels were moderate or high in 69% of wounds at baseline which decreased to 25% at final assessment (p<0.001). Suspected biofilm and local wound infection decreased from 79% and 43%, respectively, at baseline, to 18% and 3%, respectively, at final assessment (p<0.001 for both). CONCLUSION: The WHP is a new proposed standard of care that successfully treated hard-to-heal wounds by addressing the key local barriers to wound healing.

Effects of intraocular scatter on near peripheral vision.

Both cataracts and age-related macular degeneration (AMD) may occur with aging and are often developed simultaneously. We performed a study to better characterize the impact of induced scatter on the quality of vision in the near periphery, a region where individuals with AMD typically maintain their functional vision. We used an optical instrument as a cataract simulator based on projecting at the eye's pupil plane phase masks with controlled spatial properties generated with a spatial light modulator. The phase wavefronts were designed to accurately replicate the angular distribution of light intensity in the retina found in cataractous eyes with different severities. The induced amount of scatter ranged from values of straylight (S) from 10 to 85 degree2/sr, which corresponds from normal aging eye to advanced cataract stages. Mesopic visual acuity (VA) and contrast sensitivity (CS) at 3 cycles per degree were measured at the fovea and two retinal eccentricities (5 and 10 degrees in nasal visual field). We observed a consistent linear decline in VA (expressed in LogMAR) as the amount of induced scatter (quantified by the straylight parameter S) increased, both at the fovea and in the periphery. The effect of induced scattering on mesopic VA and CS at the fovea and the near periphery was evaluated. We found a relatively lower impact of scatter in the near periphery. This may explain the modest improvement in vision often found after cataract surgery in patients with AMD.

Magnetic graphene derivates for efficient herbicide removal from aqueous solution through adsorption.

2,4-Dichlorophenoxyacetic acid (2,4-D) is an herbicide and is among the most widely distributed pollutant in the environment and wastewater. Herein is presented a complete comparison of adsorption performance between two different magnetic carbon nanomaterials: graphene oxide (GO) and its reduced form (rGO). Magnetic functionalization was performed employing a coprecipitation method, using only one source of Fe2+, requiring low energy, and potentially allowing the control of the amount of incorporated magnetite. For the first time in literature, a green reduction approach for GO with and without Fe3O4, maintaining the magnetic behavior after the reaction, and an adsorption performance comparison between both carbon nanomaterials are demonstrated. The nanoadsorbents were characterized by FTIR, XRD, Raman, VSM, XPS, and SEM analyses, which demonstrates the successful synthesis of graphene derivate, with different amounts of incorporate magnetite, resulting in distinct magnetization values. The reduction was confirmed by XPS and FTIR techniques. The type of adsorbent reveals that the amount of magnetite on nanomaterial surfaces has significant influence on adsorption capacity and removal efficiency. The procedure demonstrated that the best performance, for magnetic nanocomposites, was obtained by GO∙Fe3O4 1:1 and rGO∙Fe3O4 1:1, presenting values of removal percentage of 70.49 and 91.19%, respectively. The highest adsorption capacity was reached at pH 2.0 for GO∙Fe3O4 1:1 (69.98 mg g-1) and rGO∙Fe3O4 1:1 (89.27 mg g-1), through different interactions: π-π, cation-π, and hydrogen bonds. The adsorption phenomenon exhibited a high dependence on pH, initial concentration of adsorbate, and coexisting ions. Sips and PSO models demonstrate the best adjustment for experimental data, suggesting a heterogeneous surface and different energy sites, respectively. The thermodynamic parameters showed that the process was spontaneous and exothermic. Finally, the nanoadsorbents demonstrated a high efficiency in 2,4-D adsorption even after five adsorption/desorption cycles.

Inverse-Vaccines for Rheumatoid Arthritis Re-establish Metabolic and Immunological Homeostasis in Joint Tissues.

Rheumatoid arthritis (RA) causes immunological and metabolic imbalances in tissue, exacerbating inflammation in affected joints. Changes in immunological and metabolic tissue homeostasis at different stages of RA are not well understood. Herein, the changes in the immunological and metabolic profiles in different stages in collagen induced arthritis (CIA), namely, early, intermediate, and late stage is examined. Moreover, the efficacy of the inverse-vaccine, paKG(PFK15+bc2) microparticle, to restore tissue homeostasis at different stages is also investigated. Immunological analyses of inverse-vaccine-treated group revealed a significant decrease in the activation of pro-inflammatory immune cells and remarkable increase in regulatory T-cell populations in the intermediate and late stages compared to no treatment. Also, glycolysis in the spleen is normalized in the late stages of CIA in inverse-vaccine-treated mice, which is similar to no-disease tissues. Metabolomics analyses revealed that metabolites UDP-glucuronic acid and L-Glutathione oxidized are significantly altered between treatment groups, and thus might provide new druggable targets for RA treatment. Flux metabolic modeling identified amino acid and carnitine pathways as the central pathways affected in arthritic tissue with CIA progression. Overall, this study shows that the inverse-vaccines initiate early re-establishment of homeostasis, which persists through the disease span.

CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells.

ABSTRACT: Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155/pulmonary vascular resistance (PVR), CD112/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell-based clinical trials.

Current trends and prospects in quinoa research: An approach for strategic knowledge areas.

Currently, the demand for healthy consumption and the use of alternatives to dairy proteins for the development of foods with good nutritional value are growing. Quinoa has received much attention because it contains a high content of proteins, essential amino acids, essential fatty acids, minerals, vitamins, dietary fibers, and bioactive compounds. Nevertheless, this content and the bioavailability of specific compounds of interest are related to the genotype, the agri-environmental conditions, and management practices where quinoa is grown and postharvest management. This article aimed to analyze the research trends for three knowledge areas: quinoa plant breeding for nutraceutical properties, plant-soil relations focused on abiotic stresses, and postharvest and value-added transformation activities. To this end, a specific methodological design based on bibliometrics and scientometrics methods was used. Through these analyses based on publications' keywords, titles, abstracts, and conclusions sections, for each knowledge area, the key research trends (scope and main topics), the classification of trends based on their development and relevance degree, and the core of knowledge were established. The trends comprise the current state of research. Finally, analyzing the conclusions, recommendations, and future research sections of key publications, a strong correlation among plant breeding research to obtain varieties with tolerance to biotic and abiotic stresses, nutritional and functional compounds of interest for food safety, and the development of products with higher added value established interest in further research on the potential bioactivity of quinoa and the verification of health benefits to humans.

Unraveling motor imagery brain patterns using explainable artificial intelligence based on Shapley values.

BACKGROUND AND OBJECTIVE: Motor imagery (MI) based brain-computer interfaces (BCIs) are widely used in rehabilitation due to the close relationship that exists between MI and motor execution (ME). However, the underlying brain mechanisms of MI remain not well understood. Most MI-BCIs use the sensorimotor rhythms elicited in the primary motor cortex (M1) and somatosensory cortex (S1), which consist of an event-related desynchronization followed by an event-related synchronization. Consequently, this has resulted in systems that only record signals around M1 and S1. However, MI could involve a more complex network including sensory, association, and motor areas. In this study, we hypothesize that the superior accuracies achieved by new deep learning (DL) models applied to MI decoding rely on focusing on a broader MI activation of the brain. Parallel to the success of DL, the field of explainable artificial intelligence (XAI) has seen continuous development to provide explanations for DL networks success. The goal of this study is to use XAI in combination with DL to extract information about MI brain activation patterns from non-invasive electroencephalography (EEG) signals. METHODS: We applied an adaptation of Shapley additive explanations (SHAP) to EEGSym, a state-of-the-art DL network with exceptional transfer learning capabilities for inter-subject MI classification. We obtained the SHAP values from two public databases comprising 171 users generating left and right hand MI instances with and without real-time feedback. RESULTS: We found that EEGSym based most of its prediction on the signal of the frontal electrodes, i.e. F7 and F8, and on the first 1500 ms of the analyzed imagination period. We also found that MI involves a broad network not only based on M1 and S1, but also on the prefrontal cortex (PFC) and the posterior parietal cortex (PPC). We further applied this knowledge to select a 8-electrode configuration that reached inter-subject accuracies of 86.5% ± 10.6% on the Physionet dataset and 88.7% ± 7.0% on the Carnegie Mellon University's dataset. CONCLUSION: Our results demonstrate the potential of combining DL and SHAP-based XAI to unravel the brain network involved in producing MI. Furthermore, SHAP values can optimize the requirements for out-of-laboratory BCI applications involving real users.

Exploring the chemical diversity of Capsicum chinense cultivars using NMR-based metabolomics and machine learning methods.

The habanero pepper (Capsicum chinense) is a prominent spicy fruit integral to the historical, social, cultural, and economic fabric of the Yucatan peninsula in Mexico. This study leverages the power of 1H NMR spectroscopy coupled with machine learning algorithms to dissect the metabolomic profile of eleven C. chinense cultivars, including those grown by INIFAP (Habanero-Jaguar, Antillano-HRA 1-1, Antillano-HRA 7-1, Habanero-HAm-18A, Habanero-HC-23C, and Jolokia-NJolokia-22) and commercial hybrids (Habanero-Rey Votán, Habanero-Kabal, Balam, USAPR10117, and Rey Pakal). A total of fifty metabolites, encompassing sugars, amino acids, short-chain organic acids, and nucleosides, were identified from the 1H NMR spectra. The optimized machine learning model proficiently predicted the similarity percentage between the INIFAP-grown cultivars and commercial hybrids, thereby facilitating a comprehensive comparison. Biomarkers unique to each cultivar were delineated, revealing that the Habanero-Rey Votán cultivar is characterized by the highest concentration of sugars. In contrast, the Balam cultivar is rich in amino acids and short-chain organic acids, sharing a similar metabolomic profile with the Jolokia-NJolokia-22 cultivar. The findings of this study underscore the efficacy and reliability of NMR-based metabolomics as a robust tool for differentiating C. chinense cultivars based on their intricate chemical profiles. This approach not only contributes to the scientific understanding of the metabolomic diversity among habanero peppers but also holds potential implications for food science, agriculture, and the culinary arts.

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of women's mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. METHODS: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and (5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-ß estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson's staining. RESULTS: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) -dP/dt was decreased in Ovx groups without ERT (-750 vs -1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. CONCLUSIONS: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.

Modeling Lanthanide Ions in Solution: A Versatile Force Field in Aqueous and Organic Solvents.

In this paper, we propose a new nonpolarizable force field for describing the Ln3+ (Ln = lanthanide) series based on a 12-6-4 Lennard-Jones potential. The development of the force field was performed in pure water by adjusting both the ion-oxygen distance and the hydration free energy. This force field accurately reproduces the Ln3+ hydration properties through the series, especially the coordination number that is hardly accessible using a nonpolarizable force field. Then, the validity and the transferability of the current force field were evaluated for two different systems containing Ln3+ in various solvents, namely, 0.1 mol L-1 La(NO3)3 salts in methanol and Eu(NO3)3 salts in solvent organic phases composed of DMDOHEMA molecules in n-heptane. The good agreement between our simulations and the data available in the literature confirms the accuracy of the force field for describing the lanthanide cations in both aqueous and nonaqueous media.

A comprehensive review of unmanned aerial vehicle-based approaches to support photovoltaic plant diagnosis.

Accurate photovoltaic (PV) diagnosis is of paramount importance for reducing investment risk and increasing the bankability of the PV technology. The application of fault diagnostic solutions and troubleshooting on operating PV power plants is vital for ensuring optimal energy harvesting, increased power generation production and optimised field operation and maintenance (O&M) activities. This study aims to give an overview of the existing approaches for PV plant diagnosis, focusing on unmanned aerial vehicle (UAV)-based approaches, that can support PV plant diagnostics using imaging techniques and data-driven analytics. This review paper initially outlines the different degradation mechanisms, failure modes and patterns that PV systems are subjected and then reports the main diagnostic techniques. Furthermore, the essential equipment and sensor's requirements for diagnosing failures in monitored PV systems using UAV-based approaches are provided. Moreover, the study summarizes the operating conditions and the various failure types that can be detected by such diagnostic approaches. Finally, it provides recommendations and insights on how to develop a fully functional UAV-based diagnostic tool, capable of detecting and classifying accurately failure modes in PV systems, while also locating the exact position of faulty modules.

Bacterial peritonitis secondary to Capnocytophaga canimorsus.

We present the case of a patient with liver cirrhosis and several previous episodes of ascitic decompensation, who was admitted for bacterial peritonitis secondary to Capnocytophaga canimorsus infection. The initial clinical presentation, diagnosis, treatment and resolution are described. This is the first case described of peritonitis caused by this agent in a patient with similar characteristics.

Plantar keratoderma-like crusted scabies in an immunocompetent infant after topical steroids.

A healthy 6-month-old girl presented with plantar keratoderma-like lesions unresponsive to topical corticosteroids. Nocturnal pruritus in 13 relatives, presence of burrows on clinical exam, and the positive scabies preparation led to the diagnosis of crusted scabies. She was successfully treated with topical and oral scabicides. Crusted scabies is a severe form of Sarcoptes scabiei infection uncommon in immunocompetent subjects, in whom previous corticosteroid use may favor its occurrence.

Management of Lymph Node-positive Penile Cancer: A Systematic Review.

CONTEXT: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. OBJECTIVE: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EVIDENCE ACQUISITION: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. CONCLUSIONS: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. PATIENT SUMMARY: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.

Overexpression of BAPT and DBTNBT genes in Taxus baccata in vitro cultures to enhance the biotechnological production of paclitaxel.

Paclitaxel is one of the most effective anticancer drugs ever developed. Although the most sustainable approach to its production is provided by plant cell cultures, the yield is limited by bottleneck enzymes in the taxane biosynthetic pathway: baccatin-aminophenylpropanoyl-13-O-transferase (BAPT) and 3'-N-debenzoyltaxol N-benzoyltransferase (DBTNBT). With the aim of enhancing paclitaxel production by overcoming this bottleneck, we obtained distinct lines of Taxus baccata in vitro roots, each independently overexpressing either of the two flux-limiting genes, BAPT or DBTNBT, through a Rhizobium rhizogenes A4-mediated transformation. Due to the slow growth rate of the transgenic Taxus roots, they were dedifferentiated to obtain callus lines and establish cell suspensions. The transgenic cells were cultured in a two-stage system and stimulated for taxane production by a dual elicitation treatment with 1 µm coronatine plus 50 mm of randomly methylated-ß-cyclodextrins. A high overexpression of BAPT (59.72-fold higher at 48 h) and DBTNBT (61.93-fold higher at 72 h) genes was observed in the transgenic cell cultures, as well as an improved taxane production. Compared to the wild type line (71.01 mg/L), the DBTNBT line produced more than four times higher amounts of paclitaxel (310 mg/L), while the content of this taxane was almost doubled in the BAPT line (135 mg/L). A transcriptional profiling of taxane biosynthetic genes revealed that GGPPS, TXS and DBAT genes were the most reactive to DBTNBT overexpression and the dual elicitation, their expression increasing gradually and constantly. The same genes exhibited a pattern of isolated peaks of expression in the elicited BAPT-overexpressing line.

Bacterial peritonitis secondary to Capnocytophaga canimorsus

We present the case of a patient with liver cirrhosis and several previous episodes of ascitic decompensation, who was admitted for bacterial peritonitis secondary to Capnocytophaga canimorsus infection. The initial clinical presentation, diagnosis, treatment and resolution are described. This is the first case described of peritonitis caused by this agent in a patient with similar characteristics. (AU)

Upper Limb Spasticity: The Quality of Online Patient Resources.

OBJECTIVE: The aim of the study is to assess the quality, readability, content, accessibility, and structure of online resources for patients with upper limb spasticity. DESIGN: This was a cross sectional study examined Internet searches across three search engines related to patient resources for upper limb spasticity. Search phrases for either hand or upper limb spasticity were used. The top 20 Websites from each search were evaluated using the four readability metrics and the DISCERN scale for quality assessment. YouTube videos with exact search phrases were evaluated using DISCERN. Descriptive statistical analyses were performed using SPSS software. RESULTS: Thirty-six Websites and 33 videos met the inclusion criteria for this study. The average Flesh-Kincaid Grade Level of the Websites was 11.7 ± 3.1, showing low Website readability. According to this index, only two Websites were written at the suggested sixth-grade level (5.4%). With a maximum score of 75, the mean DISCERN score for both Websites and videos scored in the "good" range (53.5 ± 8 and 50.5 ± 6.6), respectively. CONCLUSIONS: Current online resources for upper limb spasticity are good in quality but are written above the health literacy level of American citizens. Organizations should consider reviewing their present materials and developing high-quality patient education materials that are easier to understand.