Search

Abstract Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

Biosurfactants are amphipathic molecules with considerable potential for application in different industries due to their biochemical characteristics, low toxicity as well as greater biodegradability and stability compared to chemical surfactants when submitted to adverse environmental conditions. The aim of the present study was to investigate the production of a biosurfactant by Candida lipolytica UCP 0988 grown in a medium containing 4.0% molasses, 2.5% used soybean frying oil, and 2.5% corn steep liquor for 144 h at 200 rpm. The biosurfactant was characterized; its stability and toxicity were investigated, and the compound was applied in oil removal tests. In the C. lipolytica growth and biosurfactant production studies, the surface tension of the medium was reduced from 72 mN/m to 25 mN/m, the critical micellar concentration (CMC) was 0.5 g/L (w/v), and the yield was 12 g/L. Tests under extreme conditions of temperature, pH, and NaCl indicated the stability of the biosurfactant. Fourier-transform infrared and nuclear magnetic resonance spectroscopy of the chemical structure of the purified biosurfactant suggested that the biosurfactant is a glycolipid. The anionic biosurfactant exhibited no toxicity to the microcrustacean Artemia salina or vegetable seeds (Brassica oleracea). Dispersion tests in seawater demonstrated 100% efficiency of the biomolecule against motor oil. The biosurfactant was efficient at removing oil from sand in static and kinetic tests at concentrations of ½ CMC (0.25 g/L), CMC (0.5 g/L), and 2 × CMC (1.0 g/L), with removal rates of 70 to 96%, whereas the synthetic surfactants tested removed only 10 to 18% of the oil. Based on the findings, the biosurfactant analyzed has considerable potential for the remediation of contaminated coastal and marine environments due to oil spills.

In this work, a comparative study is presented to evaluate the performance of iterative methods to solve nonlinear systems applied to grid impedance estimation. The iterative methods of Newton-Raphson, Potra-Pták, and Chun were embedded in the control system of a three-phase inverter supported by a photovoltaic plant connected to the grid. The adopted impedance estimation technique consists of successive variation of the power injected into the grid, more precisely, at three different levels. The voltage and current amplitudes at the point of common coupling~(PCC) are monitored and serve as input for the iterative methods, which, after processing them, provide an estimate of the grid impedance. To compare the performance between the methods, the following merit figures were listed: execution time, number of iterations required to deliver the estimates, percentage error, efficiency index, computational efficiency, computational efficiency index, and stability of the iterative method. The results presented were obtained through real-time simulations. From that, it was possible to conclude about the method with the best performance, thus contributing to greater assertiveness on the part of designers when choosing the most efficient iterative method to be embedded in a microcontroller for grid impedance estimation purposes.

The composition of vegetation cover in Arctic environments is evolving due to climate change. This study focused on estimating carbon and nitrogen stocks in vegetation and soil for different Arctic habitats (i.e., sub-ecosystem environments) with contrasted plant communities and soil profiles, to better understand the spatial variation of these stocks and the relationships between aboveground vegetation and soil characteristics in these environments. Vegetation composition and soil characteristics were measured in different habitats in a mire and a heathland ecosystem in northern Sweden. Multivariate analyses were used to define dominant vegetation and soil profile types, and carbon and nitrogen stocks were computed and compared across these types. Shrub-dominated and graminoid-dominated vegetation types presented similar carbon stocks but different nitrogen stocks, and shrub-dominated environments presented significantly higher proportions of their stocks distributed in the long-lived (i.e., woody) compartment. Soil stocks varied considerably between ecosystems. However, no clear relationships could be established between current vegetation community composition and soil carbon and nitrogen stocks across environments. The increase in shrub or graminoid abundance may affect carbon and nitrogen cycles most through biomass distribution between plant compartments rather than through the absolute stocks they represent. Ultimately, in arctic and subarctic ecosystems experiencing climate change, the interactions between plant biomass composition and soil characteristics could have contrasted consequences for ecological functioning and C and N cycles.

El objetivo de este trabajo fue evaluar el efecto de la asociación de Leucaena leucocephala, y su co-inoculación con una cepa del hongo micorrízico arbuscular (HMA) Claroideoglomus claroideum y un aislado local de rizobio, sobre el comportamiento de las gramíneas asociadas (Bouteloua gracilis, Bouteloua curtipendula y Setaria macrostachya). Se estudiaron las estructuras micorrízicas y la nodulación. Se realizaron tres experimentos independientes, uno por cada gramínea, en asociación con L. leucocephala co-inoculada y sin inocular, o sola (como testigo). Los pastos asociados con L. leucocephala co-inoculada produjeron mayor cantidad de tallos que aquellos asociados con L. leucocephala sin inocular. B. gracilis y B. curtipendula acumularon mayor biomasa cuando se asoció con L. leucocephala co-inoculada. Las concentraciones de clorofilas a, b y totales en S. macrostachya y la de clorofila b en B. gracilis se vieron favorecidas por la asociación con L. leucocephala. La co-inoculación promovió el desarrollo de estructuras micorrízicas en la rizósfera y el número de nódulos en raíces de L. leucocephala, aunque el porcentaje de nódulos efectivos no reflejó diferencias entre tratamientos. En conclusión, la asociación de gramíneas con L. leucocephala y su inoculación con HMA y aislados de rizobios locales no solo promueve el desarrollo de estructuras micorrízicas y la nodulación, sino también aumenta el crecimiento y el contenido de pigmentos fotosintéticos en las gramíneas asociadas

Background Cerebrovascular events remain one of the most devastating complications of transcatheter aortic valve implantation (TAVI). Data from real‐world contemporary cohorts on longitudinal trends and outcomes remain limited. The aim of this study was to assess incidence, temporal trends, predictors, and outcomes of cerebrovascular events following transfemoral TAVI. Methods and Results The CENTER2 (Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Implantation With Balloon‐Expandable Valves Versus Self‐Expandable Valves 2) study includes patients undergoing TAVI between 2007 and 2022. The database contains pooled patient‐level data from 10 clinical studies. A total of 24 305 patients underwent transfemoral TAVI (mean age 81.5±6.7 years, 56% women, median Society of Thoracic Surgeon Predicted Risk of Mortality 4.9% [3.1%–8.5%]). Of these patients, 2.2% (n=534) experienced stroke in the first 30 days after TAVI, and 40 (0.4%) had a transient ischemic attack. Stroke rates remained stable during the treatment period (2007–2010: 2.1%, 2011–2014: 2.5%, 2015–2018: 2.1%, 2019–2022: 2.1%; Ptrend=0.28). Moreover, 30‐day cerebrovascular event rates were similar across Society of Thoracic Surgeon Predicted Risk of Mortality risk categories: 2.1% in low‐risk, 2.6% in intermediate‐risk, and 2.5% in high‐risk patients (P=0.21). Mortality was higher in patients with 30‐day stroke than without at 30 days (20.3% versus 4.7%; odds ratio, 5.1 [95% CI, 4.1–6.5]; P

Introduction and Objectives: Prevalence and mortality of chronic liver disease have risen significantly. In end stage liver disease, the survival of patients is approximately two years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is limited. We aim to assess associated factors and trends in palliative care use in recent years. Materials and Methods: A Multicenter retrospective cohort of patients with end stage liver disease who suffered in-hospital mortality between 2017 and 2019. Information regarding patient demographics, hospital characteristics, comorbidities, etiology, decompensations, and interventions was collected. Two-sided tests and logistic regression analysis were used to identify factors associated with palliative care use. Results: A total of 201 patients were analyzed, with a yearly increase in palliative care consultation: 26.7 % in 2017 to 38.3 % in 2019. Patients in palliative care were older (65.72 ± 11.70 vs. 62.10 ± 11.44; p = 0.003), had a lower Karnofsky functionality scale (χ=18.104; p = 0.000) and had higher rates of hepatic encephalopathy (32.1 % vs. 17.4 %, p = 0.007) and hepatocarcinoma (61.7 % vs. 26.2 %; p = 0.000). No differences were found for Model for End-stage Liver Disease (19.28 ± 6.60 vs. 19,90 ± 5.78; p = 0.507) or Child-Pugh scores (p = 0.739). None of the patients who die in the intensive care unit receive palliative care (0 % vs 31.6 %; p = 0.000). Half of the palliative care consultations occurred 6,5 days before death. Conclusions: Palliative care use differs based on demographics, disease complications, and severity. Despite its increasing implementation, palliative care intervention occurs late. Future investigations should identify approaches to achieve an earlier and concurrent care model.

Summary: The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS). We observed 117 RFS events in 664 patients with a median follow-up of 7 years. Hallmark gene set analyses showed significant association between enrichment in immune-related gene expression and favorable outcome after TAC in hormone receptor-negative, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) (triple-negative breast cancer [TNBC]). We validated this association in TNBC patients treated with TAC on H&E slides; stromal tumor-infiltrating lymphocytes (sTILs) ≥20% was associated with longer RFS (hazard ratio 0.18, p = 0.01), while in patients treated with ddAC no difference in RFS was seen (hazard ratio 0.92, p = 0.86, pinteraction = 0.02).

Sporotrichosis is a subacute to chronic mycosis caused by species of the genus Sporothrix. While the lymphocutaneous form predominates in most cases, immunocompromised individuals may present with disseminated variants. It is more prevalent in adults and rare in infants, with poorly studied risk factors and epidemiological aspects in this age group. We describe a case of sporotrichosis infection in a 9-month-old child, presenting with two progressively growing nodules, soft in consistency, located in the right cervical and pre-auricular regions, associated with a decline in general condition and fever over a month’s duration. Despite multiple oral antibiotics, there was no lesional improvement. Aspiration of one of the nodules, and culture of the secretion revealed Sporothrix. The patient was then treated with oral itraconazole, leading to regression of the lesions within 2 months. The identification of the transmission agent in this case was not possible. This report aims to broaden the understanding of sporotrichosis manifestation in infants and to provide valuable insights for the enhancement of specific preventive, diagnostic, and therapeutic strategies for this age group of dermatological patients.

It is estimated that approximately one month after radical prostatectomy, a surgical procedure to remove the prostate, 80% of men experience urinary incontinence (UI). Behavioral therapy, which involves modifying the patient’s lifestyle habits, along with physical treatments such as exercises to strengthen the pelvic muscles and complementary behavioral therapies with techniques associated with personal beliefs, can be used to treat urinary incontinence in this context. IUProst® is a mobile health application (mHealth) designed to promote self-care and improve the quality of life for men who suffer from urinary incontinence due to prostate removal surgery caused by prostate cancer. Version 2.0 of IUProst® was released with several improvements, including adding gamification elements to encourage patient engagement in the execution of behavioral treatment exercises for urinary incontinence. This article presents the IUProst® application and analyzes the data generated by its use to understand the level of improvement that patients have experienced regarding urinary incontinence. It also examines the impact of gamification on exercise execution. The results demonstrate the clinical improvement in patients’ involuntary loss of urine, presenting less urine flow and reducing the feeling of urgency to go to the bathroom after using IUProst®. A comparative analysis is also included, considering the 60 days before and after the implementation of the gamification elements. During the 120 days considered, gamified data was collected for 60 days, and this period accounted for 83% of all exercises performed, despite the similar number of users using the application. The significant increase in exercise performance during the gamified period suggests that the gamification positively supported patient engagement.

The present study investigated the effects of the commercial biopreservatives FRESHQ-11 (Lactobacillus rhamnosus), labeled as F, and HOLDBAC YM-B LYO 100 DCU (Lactobacillus rhamnosus and Propionibacterium freudenreichii subsp. shermanii), labeled as H, at different dosages on the pH, titratable acidity (%), fungal inhibition, and textural parameters of yogurt during 28 days of storage at 7 ± 1 °C. The study compared these biopreservatives with yogurt containing only the chemical preservative potassium sorbate at the maximum allowed concentration (C1) and yogurt without any chemical preservatives (C2), with the goal of identifying alternatives to reduce or replace potassium sorbate. Yogurts were formulated with biopreservatives at concentrations of 0.1% and 0.2% (v/v) and with potassium sorbate at 0.015% and 0.03%. The results indicated that yogurts containing biopreservatives had significantly lower pH and higher titratable acidity (%) than C2 (p < 0.05). Syneresis significantly decreased over the 28-day storage period at 7 ± 1 °C (p < 0.05). Additionally, yogurts with bioprotective cultures exhibited significantly lower textural parameters (p < 0.05) compared to C1 and C2. This study underscores the potential of biopreservatives as viable replacements for potassium sorbate, with these formulations being comparable to C1 in inhibiting molds and yeasts, particularly when L. rhamnosus was used at 0.2% v/v. This finding is promising for future pilot and industrial-scale applications.

This study investigated the effects of fermenting plum pulp with Bifidobacterium animalis ssp. lactis (BAL) on its physicochemical and bioactive properties, as well as the optimization of the freeze-drying (FD) process to develop a fruit-based probiotic delivery system. Fermentation significantly reduced the pH and total acidity of the pulp, achieving a cell viability of 11 log CFU/mL. The FD process was optimized using a factorial design, with maltodextrin concentration (3, 5, and 7%) and freezing temperature (−150, −100, and −50 °C) as variables. The P2 experiment, which used 7% maltodextrin and freezing at −150 °C, showed the best results in terms of yield (25.67%), cell viability (8 log CFU/g), and probiotic survival rate (97.66%). Samples P5, P6, and P7, prepared with 5% maltodextrin and freezing at −100 °C, exhibited the highest levels of bioactive compounds and antioxidant activity (p < 0.05). During 28 days of storage, all samples maintained cell viability without significant logarithmic reduction. In summary, probiotic plum powders offer an excellent plant-based alternative for probiotic consumption, providing safe levels of beneficial bacteria and bioactive compounds with antioxidant action, meeting health and nutrition needs.

The twelve cranial nerves play a crucial role in the nervous system, orchestrating a myriad of functions vital for our everyday life. These nerves are each specialized for particular tasks. Cranial nerve I, known as the olfactory nerve, is responsible for our sense of smell, allowing us to perceive and distinguish various scents. Cranial nerve II, or the optic nerve, is dedicated to vision, transmitting visual information from the eyes to the brain. Eye movements are governed by cranial nerves III, IV, and VI, ensuring our ability to track objects and focus. Cranial nerve V controls facial sensations and jaw movements, while cranial nerve VII, the facial nerve, facilitates facial expressions and taste perception. Cranial nerve VIII, or the vestibulocochlear nerve, plays a critical role in hearing and balance. Cranial nerve IX, the glossopharyngeal nerve, affects throat sensations and taste perception. Cranial nerve X, the vagus nerve, is a far-reaching nerve, influencing numerous internal organs, such as the heart, lungs, and digestive system. Cranial nerve XI, the accessory nerve, is responsible for neck muscle control, contributing to head movements. Finally, cranial nerve XII, the hypoglossal nerve, manages tongue movements, essential for speaking, swallowing, and breathing. Understanding these cranial nerves is fundamental in comprehending the intricate workings of our nervous system and the functions that sustain our daily lives.

Abstract Background Invasive breast cancer patients are increasingly being treated with neoadjuvant chemotherapy; however, only a fraction of the patients respond to it completely. To prevent overtreatment, there is an urgent need for biomarkers to predict treatment response before administering the therapy. Methods In this retrospective study, we developed hypothesis-driven interpretable biomarkers based on deep learning, to predict the pathological complete response (pCR, i.e., the absence of tumor cells in the surgical resection specimens) to neoadjuvant chemotherapy solely using digital pathology H&E images of pre-treatment breast biopsies. Our approach consists of two steps: First, we use deep learning to characterize aspects of the tumor micro-environment by detecting mitoses and segmenting tissue into several morphology compartments including tumor, lymphocytes and stroma. Second, we derive computational biomarkers from the segmentation and detection output to encode slide-level relationships of components of the tumor microenvironment, such as tumor and mitoses, stroma, and tumor infiltrating lymphocytes (TILs). Results We developed and evaluated our method on slides from n = 721 patients from three European medical centers with triple-negative and Luminal B breast cancers and performed external independent validation on n = 126 patients from a public dataset. We report the predictive value of the investigated biomarkers for predicting pCR with areas under the receiver operating characteristic curve between 0.66 and 0.88 across the tested cohorts. Conclusion The proposed computational biomarkers predict pCR, but will require more evaluation and finetuning for clinical application. Our results further corroborate the potential role of deep learning to automate TILs quantification, and their predictive value in breast cancer neoadjuvant treatment planning, along with automated mitoses quantification. We made our method publicly available to extract segmentation-based biomarkers for research purposes.

Abstract Background Despite major improvements in treatment of HER2-positive metastatic breast cancer (MBC), only few patients achieve complete remission and remain progression free for a prolonged time. The tumor immune microenvironment plays an important role in the response to treatment in HER2-positive breast cancer and could contain valuable prognostic information. Detailed information on the cancer-immune cell interactions in HER2-positive MBC is however still lacking. By characterizing the tumor immune microenvironment in patients with HER2-positive MBC, we aimed to get a better understanding why overall survival (OS) differs so widely and which alternative treatment approaches may improve outcome. Methods We included all patients with HER2-positive MBC who were treated with trastuzumab-based palliative therapy in the Netherlands Cancer Institute between 2000 and 2014 and for whom pre-treatment tissue from the primary tumor or from metastases was available. Infiltrating immune cells and their spatial relationships to one another and to tumor cells were characterized by immunohistochemistry and multiplex immunofluorescence. We also evaluated immune signatures and other key pathways using next-generation RNA-sequencing data. With nine years median follow-up from initial diagnosis of MBC, we investigated the association between tumor and immune characteristics and outcome. Results A total of 124 patients with 147 samples were included and evaluated. The different technologies showed high correlations between each other. T-cells were less prevalent in metastases compared to primary tumors, whereas B-cells and regulatory T-cells (Tregs) were comparable between primary tumors and metastases. Stromal tumor-infiltrating lymphocytes in general were not associated with OS. The infiltration of B-cells and Tregs in the primary tumor was associated with unfavorable OS. Four signatures classifying the extracellular matrix of primary tumors showed differential survival in the population as a whole. Conclusions In a real-world cohort of 124 patients with HER2-positive MBC, B-cells, and Tregs in primary tumors are associated with unfavorable survival. With this paper, we provide a comprehensive insight in the tumor immune microenvironment that could guide further research into development of novel immunomodulatory strategies. Graphical Abstract

Surfactants can be used as nanoparticle stabilizing agents. However, since synthetic surfactants are not economically viable and environmentally friendly, biosurfactants are emerging as a green alternative for the synthesis and stabilization of nanoparticles. Nanoparticles have been applied in several areas of industry, such as the production of biomedical and therapeutic components, packaging coating, solar energy generation and transmission and distribution of electrical energy, among others. The aim of this study was to synthesize, in a simple and green way, silver nanoparticles (AgNPs) using the biosurfactant produced by Candida lipolytica UCP 0899 as a stabilizer. AgNPs were examined and morphologically characterized using the techniques of ultraviolet–visible spectroscopy (UV–visible), scanning electron microscopy (SEM), zeta potential and energy dispersive X-ray spectroscopy (EDS). Newly formed silver nanoparticles showed a maximum UV–visible absorption peak at 400 nm, while a shift to 410 nm was observed in those stored for 120 days. SEM micrograph confirmed the formation of nanoparticles with an average size of 20 nm and with a predominant spherical structure, while a zeta potential of −60 mV suggested that the use of the biosurfactant promoted their stability. Stabilized nanoparticles were tested for their antimicrobial activity against bacterial isolates of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Enterobacter sp., as well as fungal isolates of Candida albicans and Aspergillus niger. At a concentration of 16.50 µg/mL, AgNPs inhibited the growth of all target microorganisms according to the following decreasing order: E. coli (95%), S. aureus, C. albicans (90%), A. niger (85%), Enterobacter sp. (75%) and P. aeruginosa (71%). These results suggest the potential use of the biosurfactant as a stabilizer of silver nanoparticles as an antimicrobial agent in different industrial sectors. Furthermore, the in vivo toxicity potential of biosurfactants was evaluated using the Tenebrio molitor model. The larvae were treated with concentrations in the range of 2.5, 5.0 and 10 g/L, and no mortality was observed within the 24 to 72 h period, demonstrating non-toxicity within the tested concentration range. These findings support the safety, efficacy and non-toxicity of biosurfactant-stabilized nanoparticles.

Plant-derived biosurfactants are widely used due to their emulsifying and surface-active properties and can be applied in various products. The aim of this present study was to develop a mouthwash using chitosan hydrochloride and saponins extracted from the plants Chenopodium quinoa and Glycine max. After extraction of the biosurfactants using the Soxhlet method, they were characterized with the aid of infrared spectroscopy and subjected to determination of critical micelle concentration, which was found to be 4.0 and 3.5 g/L for C. quinoa and G. max, respectively. The stability of the emulsions was investigated in the presence of different oils and at different values of temperature, pH, and salinity, which showed an emulsification index greater than 40% under all conditions analyzed. After obtaining the mouthwash formulation, tests of foaming capacity, pH, and genotoxicity were performed in cells of onion (Allium cepa) roots. No presence of micronuclei was found in the roots exposed to the formulation, which indicates that there was no aggression to the cells. The results of antimicrobial susceptibility tests revealed bacteriostatic/bactericidal activity as well as antibiofilm activity of formulations against the microorganisms tested. In conclusion, the biosurfactants present in extracts from C. quinoa and G. max were found to be stable, non-toxic molecules with antimicrobial activity, with potential to replace toxic emulsifying agents commonly used in commercial products.

Arbuscular mycorrhizal fungi (AMF) play a crucial role in the resilience of plants subjected to water deficit. The objective of this study was to evaluate the impact of AMF from a semi-arid and humid ecosystem, applied as inocula (two monospecific and two consortia), and three irrigation doses (100%, 85%, and 70%) on tomato plant growth. A factorial experiment in a completely randomized design was used. Colonization with monospecific inocula (EH and ES) showed contrasting differences at 85% and 100% irrigation rates. With gradually increasing irrigation rates, colonization decreased with the CH consortium, while the CS consortium showed similar colonization levels at all three irrigation rates. AMF from humid environments (monospecific or in a consortium) did not affect equatorial diameter when the irrigation rate was reduced by 15%, while polar diameter was similar at all three irrigation rates. Inocula from the semi-arid ecosystem promoted the greatest equatorial and polar diameters at the 100% irrigation dose. The monospecific inoculum of C. etunicatum (ES) showed great potential to promote plant growth and development at the 100% irrigation dose and could be a biotechnological tool to improve tomato yield under conditions similar to those of this study.

Abstract Nanofertilizers could promote nutrient efficiency with slow release compared to conventional fertilizers (CF). Most of the applied nitrogen is lost on the soil by leaching, due to the rapid release behavior of CF. Clays can function as a nanosized porous structure to retain and slowly release nutrients. The objective of this study was to evaluate a nitrogenous nanocomposite (NCN) and its effect on leaching and N content of lettuce (Lactuca sativa). The treatments applied were: 100% conventional fertilizer, 100% nitrogenous nanocomposite and the mixture in percentage of CF/NCN 25/75, 50/50, 75/25 and 25/0, 50/0 75/0% on columns of soil with lettuce for 45 days. Leachates at the end of the cycle increased in treatments with NCN. Treatments with NCN have higher N content in the leaf. In regard to biomass growth, leaf area, leaf N, drained variables, electrical conductivity and NO3 − content, it was possible to show that the doses of 50 and 75% of NCN match the characteristics of the crop compared to the control, which allows us to use lower doses than those recommended with CFs.

The underrepresentation of the female population in exercise sciences could be attributed, at least in part, to difficulty in appropriately accounting for the effects of the menstrual cycle (MC). Previous studies examining the effects of the MC on aerobic performance and subjective measures of aerobic performance show conflicting results.Purpose: The study examined how the MC affects the objective and subjective measures of aerobic performance within untrained female participants and in comparison with untrained male participants assessed at similar time intervals.Methods: Twenty-one participants (12 females and 9 males) completed a graded exercise test (GXT) on a cycle ergometer. The female participants were tested during their early follicular (EF; menses), ovulatory (O), and mid-luteal (ML) phases of the MC. The male participants were included as the control group and were randomly assigned to a menstrual cycle phase for each visit. During GXT, maximal oxygen consumption (VO2max), respiratory exchange ratio (RER), maximal heart rate (HRmax), peak blood lactate, and rating of perceived exertion (RPE) were determined. Twenty-four hours post-exercise, the perceived recovery status (PRS) was assessed. The MC phase was estimated using basal body temperature (BBT) in the female participants.Results: The male participants obtained a higher peak power and VO2max compared to the female participants (p < 0.05). All objective measures of aerobic performance did not significantly differ across the MC phases or time points that were tested. In the untrained female participants, an effect of the MC phase on RPE was found, with RPE being higher at EF (8.92 ± 0.79) compared to O (7.67 ± 1.23; p < 0.05) and ML (7.75 ± 1.06; p < 0.05). In addition, an effect of the MC phase on PRS was found, with perceived recovery being lower at EF (6.83 ± 0.94) compared to O (8.83 ± 1.12) and ML (8.67 ± 0.65; all p < 0.005) for the untrained female participants. No significant differences in RPE and PRS were found between tests in the untrained male participants. The female participants had lower perceived recovery following EF (6.83 ± 0.94) compared with the male participants (9.00 ± 1.00; p < 0.001).Conclusion: The untrained female participants perceived greater exertion during GXT and impaired recovery following GXT in EF compared to O and ML. These results may be attributed to either a drop in female sex hormone concentrations or discomfort associated with menses. The male participants did not exhibit any changes over time. Future studies using subjective parameters such as perceived exertion to track the internal load of training in the naturally menstruating female population should consider menses.

Recent discoveries of Earth-sized planets transiting nearby M dwarfs have made it possible to characterize the atmospheres of terrestrial planets via follow-up spectroscopic observations. However, the number of such planets receiving low insolation is still small, limiting our ability to understand the diversity of the atmospheric composition and climates of temperate terrestrial planets. We report the discovery of an Earth-sized planet transiting the nearby (12 pc) inactive M3.0 dwarf Gliese 12 (TOI-6251) with an orbital period ( P _orb ) of 12.76 days. The planet, Gliese 12 b, was initially identified as a candidate with an ambiguous P _orb from TESS data. We confirmed the transit signal and P _orb using ground-based photometry with MuSCAT2 and MuSCAT3, and validated the planetary nature of the signal using high-resolution images from Gemini/NIRI and Keck/NIRC2 as well as radial velocity (RV) measurements from the InfraRed Doppler instrument on the Subaru 8.2 m telescope and from CARMENES on the CAHA 3.5 m telescope. X-ray observations with XMM-Newton showed the host star is inactive, with an X-ray-to-bolometric luminosity ratio of $\mathrm{log}{L}_{{\rm{X}}}/{L}_{\mathrm{bol}}\approx -5.7$ . Joint analysis of the light curves and RV measurements revealed that Gliese 12 b has a radius of 0.96 ± 0.05 R _⊕ , a 3 σ mass upper limit of 3.9 M _⊕ , and an equilibrium temperature of 315 ± 6 K assuming zero albedo. The transmission spectroscopy metric (TSM) value of Gliese 12 b is close to the TSM values of the TRAPPIST-1 planets, adding Gliese 12 b to the small list of potentially terrestrial, temperate planets amenable to atmospheric characterization with JWST.

Abstract Immune checkpoint blockade (ICB) is currently approved for patients with triple-negative breast cancer (TNBC), whereas responses to ICB are also observed in a small subgroup of Estrogen Receptor (ER)-positive breast cancer. The cut-off for ER-positivity (≥1%) is based on likelihood of endocrine treatment response, but ER-positive breast cancer represents a very heterogeneous group. This raises the question whether selection based on ER-negativity should be revisited to select patients for ICB treatment in the context of clinical trials. Stromal tumor-infiltrating lymphocytes (sTILs) and other immune parameters are higher in TNBC compared to ER-positive breast cancer, but it is unknown whether lower ER levels are associated with more inflamed tumor microenvironments (TME). We collected a consecutive series of primary tumors from 173 HER2-negative breast cancer patients, enriched for tumors with ER expression between 1 and 99% and found levels of stromal TILs, CD8 + T cells, and PD-L1 positivity in breast tumors with ER 1–9% and ER 10–50% to be comparable to tumors with ER 0%. Expression of immune-related gene signatures in tumors with ER 1–9% and ER 10–50% was comparable to ER 0%, and higher than in tumors with ER 51–99% and ER 100%. Our results suggest that the immune landscape of ER low tumors (1–9%) and ER intermediate tumors (10–50%) mimic that of primary TNBC.

The present review highlights the potential of insect-based proteins to address the growing need for sustainable and secure food systems. The key findings suggest that edible insects offer a viable and environmentally friendly alternative to traditional livestock, requiring significantly less land, water, and feed while emitting lower levels of greenhouse gases. Insect farming can also reduce waste and recycle nutrients, supporting circular economy models. Nutritionally, insects provide high-quality protein, essential amino acids, and beneficial fats, making them valuable to human diets. Despite these benefits, this review emphasizes the need for comprehensive regulatory frameworks to ensure food safety, manage potential allergenicity, and mitigate contamination risks from pathogens and environmental toxins. Additionally, developing innovative processing technologies can enhance the palatability and marketability of insect-based products, promoting consumer acceptance. This review concludes that with appropriate regulatory support and technological advancements, insect-based proteins have the potential to significantly contribute to global food security and sustainability efforts.

High blood cholesterol levels are a major risk factor for cardiovascular diseases. A purified aqueous extract of Fucus vesiculosus, rich in phlorotannins and peptides, has been described for its potential to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells’ metabolites and proteins was analysed to gain a deeper understanding of its mode of action on lipids’ metabolism, particularly concerning the absorption and transport of exogenous cholesterol. Caco-2 cells, differentiated into enterocytes, were exposed to the extract, and analysed by untargeted metabolomics and proteomics. The results of the metabolomic analysis showed statistically significant differences in glutathione content of cells exposed to the extract compared to control cells, along with an increased expression of fatty acid amides in exposed cells. A proteomic analysis showed an increased expression in cells exposed to the extract compared to control cells of FAB1 and NPC1, proteins known to be involved in lipid metabolism and transport. To the extent of our knowledge, this study is the first use of untargeted metabolomics and a proteomic analysis to investigate the effects of F. vesiculosus on differentiated Caco-2 cells, offering insights into the molecular mechanism of the extract’s compounds on intestinal cells.

Abstract Introduction: End of life care of patients with end-stage kidney disease (ESKD) may be particularly challenging and requires the intervention of a specialized palliative care team (PCT). Objective: To characterize the population of ESKD patients referred to a PCT and evaluate the determinants of planned dying at home. Methods: We performed a retrospective observational cohort study of all patients with ESKD referred to our PCT between January 2014 and December 2021 (n = 60) and further characterized those with previously known ESKD regarding place of death (n = 53). Results: The majority of the patients were female and the median age was 84 years. Half of the patients were on conservative treatment, 43% were on chronic hemodialysis, and the remainder underwent hemodialysis on a trial basis and were subsequently suspended. Of those with previously known ESKD, 18% died at home and neither gender, age, cognition, performance status, comorbidities, CKD etiology, or treatment modality were associated with place of death. Anuria was significantly associated with dying at the hospital as was shorter time from dialysis suspension and death. Although not reaching statistical significance, we found a tendency towards a longer duration of palliative care follow-up in those dying at home. Conclusion: Dying at home is possible in a palliative domiciliary program regardless of age, gender, etiology of CKD, major comorbidities, and treatment modality. Anuria and shorter survival from RRT withdrawal may be limiting factors for planned dying at home. A longer follow-up by palliative care may favor dying at home.

Abstract Accurately determining the molecular subtypes of breast cancer is important for the prognosis of breast cancer patients and can guide treatment selection. In this study, we develop a deep learning-based model for predicting the molecular subtypes of breast cancer directly from the diagnostic mammography and ultrasound images. Multi-modal deep learning with intra- and inter-modality attention modules (MDL-IIA) is proposed to extract important relations between mammography and ultrasound for this task. MDL-IIA leads to the best diagnostic performance compared to other cohort models in predicting 4-category molecular subtypes with Matthews correlation coefficient (MCC) of 0.837 (95% confidence interval [CI]: 0.803, 0.870). The MDL-IIA model can also discriminate between Luminal and Non-Luminal disease with an area under the receiver operating characteristic curve of 0.929 (95% CI: 0.903, 0.951). These results significantly outperform clinicians’ predictions based on radiographic imaging. Beyond molecular-level test, based on gene-level ground truth, our method can bypass the inherent uncertainty from immunohistochemistry test. This work thus provides a noninvasive method to predict the molecular subtypes of breast cancer, potentially guiding treatment selection for breast cancer patients and providing decision support for clinicians.

Abstract In prior clinical studies, levocetirizine (LEVO) has demonstrated no effect on ventricular repolarization (QTc intervals), therefore it is a relevant negative control to assess in nonclinical assays to define low proarrhythmic risk. LEVO was tested in beagle dog and cynomolgus monkey (nonhuman primate [NHP]) telemetry models to understand the nonclinical‐clinical translation of this negative control. One oral dose of vehicle, LEVO (10 mg/kg/species) or moxifloxacin (MOXI; 30 mg/kg/dog; 80 mg/kg/NHP) was administered to instrumented animals (N = 8/species) using a cross‐over dosing design; MOXI was the in‐study positive control. Corrected QT interval values (QTcI) were calculated using an individual animal correction factor. Blood samples were taken for drug exposure during telemetry and for pharmacokinetic (PK) analysis (same animals; different day) for exposure‐response (C‐QTc) modeling. Statistical analysis of QTc‐by‐timepoint data showed that LEVO treatment was consistent with vehicle, thus no effect on ventricular repolarization was observed over 24 h in both species. PK analysis indicated that LEVO‐maximum concentration levels in dogs (range: 12,300–20,100 ng/ml) and NHPs (range: 4090–12,700 ng/ml) were ≥4‐fold higher than supratherapeutic drug levels in clinical QTc studies. Slope analysis values in dogs (0.00019 ms/ng/ml) and NHPs (0.00016 ms/ng/ml) were similar to the human C‐QTc relationship and indicated no relationship between QTc intervals and plasma levels of LEVO. MOXI treatment caused QTc interval prolongation (dog: 18 ms; NHP: 29 ms). The characterization of LEVO in these non‐rodent telemetry studies further demonstrates the value and impact of the in vivo QTc assay to define a “no QTc effect” profile and support clinical safety assessment.

Abstract To guide the choice of treatment, every new breast cancer is assessed for aggressiveness (i.e., graded) by an experienced histopathologist. Typically, this tumor grade consists of three components, one of which is the nuclear pleomorphism score (the extent of abnormalities in the overall appearance of tumor nuclei). The degree of nuclear pleomorphism is subjectively classified from 1 to 3, where a score of 1 most closely resembles epithelial cells of normal breast epithelium and 3 shows the greatest abnormalities. Establishing numerical criteria for grading nuclear pleomorphism is challenging, and inter-observer agreement is poor. Therefore, we studied the use of deep learning to develop fully automated nuclear pleomorphism scoring in breast cancer. The reference standard used for training the algorithm consisted of the collective knowledge of an international panel of 10 pathologists on a curated set of regions of interest covering the entire spectrum of tumor morphology in breast cancer. To fully exploit the information provided by the pathologists, a first-of-its-kind deep regression model was trained to yield a continuous scoring rather than limiting the pleomorphism scoring to the standard three-tiered system. Our approach preserves the continuum of nuclear pleomorphism without necessitating a large data set with explicit annotations of tumor nuclei. Once translated to the traditional system, our approach achieves top pathologist-level performance in multiple experiments on regions of interest and whole-slide images, compared to a panel of 10 and 4 pathologists, respectively.

Aim of study: We evaluated the use of oat grain as an alternative source of energy to maize grain in high energy finishing diets. Maize crop production in arid and semi-arid areas is poor or non-existent. Thus, small grains such as oats have become an alternative in high energy rations due to their versatility and ease of cultivation. Area of study: Semiarid region of Buenos Aires province, Argentina Material and methods: Sixteen Angus steers were randomly assigned to two dietary treatments based on whole oats grain (OD) or whole maize grain (MD) for 61 days. Diets were formulated iso-nitrogenous and iso-energetic. Animal performance, carcass attributes and beef quality traits were evaluated. Longissimus thoracis steaks were wet-aged at 4°C for either 4 or 14 days. Main results: Similar results were found between OD and MD for the variables of performance, carcass evaluation and water retention in fresh meat. No interactions between diet and ageing period were found for any of the variables evaluated. The MD beef was lighter and had a redder appearance than the OD beef. The 4 days-aged beef showed higher values of L*, a* and b* and was more saturated than the 14 days-aged beef. However, the perception of beef colour by the human eye, evaluated through the CIEDE2000 metric, showed no differences among diets and ageing periods. Research highlights: Oat grain could be used in replacement of maize grain as an energy source in fattening rations of beef cattle, obtaining similar animal performance and meat quality.

TOI-6255 b (GJ 4256) is an Earth-sized planet (1.079 ± 0.065 R _⊕ ) with an orbital period of only 5.7 hr. With the newly commissioned Keck Planet Finder and CARMENES spectrographs, we determine the planet’s mass to be 1.44 ± 0.14 M _⊕ . The planet is just outside the Roche limit, with P _orb / P _Roche = 1.13 ± 0.10. The strong tidal force likely deforms the planet into a triaxial ellipsoid with a long axis that is ∼10% longer than the short axis. Assuming a reduced stellar tidal quality factor ${Q}_{\star }^{{\prime} }\approx {10}^{7}$ , we predict that tidal orbital decay will cause TOI-6255 to reach the Roche limit in roughly 400 Myr. Such tidal disruptions may produce the possible signatures of planet engulfment that have been seen on stars with anomalously high refractory elemental abundances compared to their conatal binary companions. TOI-6255 b is also a favorable target for searching for star–planet magnetic interactions, which might cause interior melting and hasten orbital decay. TOI-6255 b is a top target (with an Emission Spectroscopy Metric of about 24) for phase-curve observations with the James Webb Space Telescope.

Abstract Hypoxia promotes aggressive tumor phenotypes and mediates the recruitment of suppressive T cells in invasive breast carcinomas. We investigated the role of hypoxia in relation to T-cell regulation in ductal carcinoma in situ (DCIS). We designed a deep learning system tailored for the tissue architecture complexity of DCIS, and compared pure DCIS cases with the synchronous DCIS and invasive components within invasive ductal carcinoma cases. Single-cell classification was applied in tandem with a new method for DCIS ductal segmentation in dual-stained CA9 and FOXP3, whole-tumor section digital pathology images. Pure DCIS typically has an intermediate level of colocalization of FOXP3+ and CA9+ cells, but in invasive carcinoma cases, the FOXP3+ (T-regulatory) cells may have relocated from the DCIS and into the invasive parts of the tumor, leading to high levels of colocalization in the invasive parts but low levels in the synchronous DCIS component. This may be due to invasive, hypoxic tumors evolving to recruit T-regulatory cells in order to evade immune predation. Our data support the notion that hypoxia promotes immune tolerance through recruitment of T-regulatory cells, and furthermore indicate a spatial pattern of relocalization of T-regulatory cells from DCIS to hypoxic tumor cells. Spatial colocalization of hypoxic and T-regulatory cells may be a key event and useful marker of DCIS progression.

Metabolic reprogramming is associated with cancer development and therapy resistance. Here, the authors show that downregulation of the serine biosynthesis enzyme PHGDH in a fraction of patients is associated with relapse in platinum-treated ovarian cancers and to NAD+ and PARP activity upregulation.

Microfouling is the deposition of inorganic and organic material on surfaces and can cause economic losses. This deposition affects the performance of vessels, causes corrosion, clogging of equipment and contaminates the surfaces of medical items and the surface of machinery that handles food; it is controlled by cleaning products that contain synthetic surfactants in their formulations. Biobased products provide a promising basis to produce sustainable chemicals such as surfactants. In the present study, the biobased surfactants glyceryl laurate and hydroxystearic acid were synthesized and evaluated for stability at different pH values, salinity and temperatures. In addition, bioactivity tests against Pseudomonas aeruginosa (UCP 0992) and Bacillus cereus (UCP 1516) were also performed. Biobased surfactants glyceryl laurate and hydroxystearic acid showed excellent stability against temperature, pH, salinity and emulsifying activities for different kinds of oils; prevented bacterial adhesion by almost 100%; and affected the production of EPS by both bacteria and their consortium when compared to a synthetic surfactant SDS. The results showed the potential of these substances for application as an alternative antifouling non-biocide.

Despite activities of daily living being frequently performed simultaneously with a cognitive task, motor function is often investigated in isolation, which can hinder the applicability of findings. This brief review presents evidence that 1) performing a cognitive challenge simultaneously with a motor task can negatively impact force steadiness and fatigability of limb muscles during a static contraction, 2) the negative impact on old adults (>65 years old), particularly older women is greater than young when a cognitive challenge is simultaneously performed with a static motor task, 3) age-related mechanisms potentially explain impairments in motor performance in the presence of a cognitive challenge, and 4) the mechanisms for the age-related decrements in motor performance can be distinct between men and women. These observations are highly relevant to the older adults, given the increased risk of accidents and injury when a motor task is performed with a high cognitive-demand task, especially in light of the expanding reliance on an aging workforce.

Introduction: Heart failure is a prevalent clinical syndrome with high morbidity and mortality rates. Palliative care has an important role in symptomatic control. This study was designed to characterize the population referred to a palliative care unit and to identify those who benefit from early and regular intervention. Aims: To characterize heart failure patients referred to a Palliative Care Team and identify those who would benefit from a regular intervention. Methods: We performed a retrospective analysis of all the heart failure patients referred to our palliative care team between January 2015 and December 2017. Results: A total of 54 patients were included with a mean age of 80 years. The mean score on the Palliative Performance Scale was 57. The median duration of disease was 46 months, 61.1% of patients were in NYHA class III, 57.4% had ejection fraction >40%, and 51.9% had ischemic cardiomyopathy. Most patients (94.4%) were referred during hospitalization; 60.8% were discharged, half with home-based assistance. Mortality one month after referral was 53.7%, and 83.3% after six months. We found no variables predictive of mortality within a month of referral. Conclusions: This study contributes to the characterization of the heart failure population referred to palliative care. No clinical sign was predictive of one-month mortality, but the high mortality rate shows that patients are referred in advanced stages of the disease or frailty. Resumo: Introdução: A insuficiência cardíaca (IC) é uma síndrome clínica prevalente e responsável por elevada morbimortalidade. Os cuidados paliativos têm um papel importante no controlo sintomático destes doentes. Objetivo: Caracterização dos doentes com IC referenciados a uma equipa de Cuidados Paliativos e identificação daqueles que beneficiam de uma intervenção mais precoce e regular. Métodos: Realizada uma análise retrospetiva de todos os doentes referenciados à equipa de cuidados paliativos entre janeiro de 2015 e dezembro de 2017. Resultados: Foram incluídos 54 doentes, com idade média de 80 anos. A palliative performance scale média era de 57. A IC tinha uma mediana de 46 meses de evolução, com uma classe funcional de NYHA de III em 61,1% dos doentes e fração de ejeção do ventrículo esquerdo >40% em 57,4%. A cardiopatia isquémica era a etiologia em 51,9% dos casos. A maioria dos doentes (94,4%) foi referenciada a partir do internamento. Desses, foi possível a alta hospitalar em 60,8% dos casos, tendo metade mantido acompanhamento domiciliário e os restantes, seguimento em consulta externa. A mortalidade a 30 dias foi de 53,7% e aos seis meses de 83,3%. Nenhuma variável mostrou relação estatisticamente significativa com a mortalidade no primeiro mês. Conclusões: Este trabalho contribuiu para a caracterização dos doentes com insuficiência cardíaca referenciados a uma equipa de cuidados paliativos. Não foram documentados sinais clínicos preditores de mortalidade no primeiro mês após referenciação à equipa. A elevada mortalidade no primeiro mês sugere que os doentes são referenciados em fases da doença avançadas ou de elevada fragilidade.

The objective of this work was to evaluate the effect of the simple and combined inoculation with three local rhizobia isolates (R1, R2 and R3) and two species of arbuscular mycorrhizal fungi (Glomus cubense -AMF1- and Claroideoglomus claroideum -AMF2-) on mycorrhizal colonization, nodulation, growth and biomass production of Leucaena leucocephala in a substrate with a close to neutrality pH under greenhouse conditions. Thirteen treatments were evaluated in a completely randomized design with five replications. The inoculation and co-inoculation promoted greater plant growth with respect to the control without inoculation and to the fertilization treatment. Within the inoculation and co-inoculation treatments, one rhizobium isolate (R2) stood out for producing the highest plant height and leaflet production, while the R3 + AMF1 and R3 + AMF2 combinations promoted the highest plant height, and also promoted higher biomass together with R1 + AMF1. In addition, the R3 + AMF2 combination stood out for presenting a high number of AMF spores, frequency and intensity by AMF colonization, and nodule activity. It is concluded that inoculation with local rhizobia isolates and their combination with AMF favors the development of mycorrhizal structures, nodulation, growth and biomass production of L. leucocephala grown in a substrate with neutral pH. Isolate R2 and the combination R3 + AMF2 were identified as effective inoculants to increase plant growth.

This study presents the development and characterization of a novel buffalo Petit Suisse cheese, enhanced with symbiotic properties through an innovative whey retention method and incorporating inulin and xanthan gum. The research focused on assessing the cheese’s physicochemical properties, shelf life, lactic acid bacteria viability, syneresis behavior, and the impact of varying concentrations of functional ingredients. The addition of inulin and xanthan gum, following a design of experiments, significantly influenced the cheese’s texture and consistency. Higher inulin concentrations were associated with increased fermentation activity, as indicated by total titratable acidity, which showed an increase from 1.22% to 1.50% over a 28-day period, and pH levels that decreased from 3.33 to 2.96. The syneresis index varied across trials, with the highest reduction observed in trials with increased xanthan gum concentrations, effectively reducing syneresis to 0%. Lactic acid bacteria viability also showed notable variations, with the highest cell survival percentage reaching 107.89% in formulations with higher inulin and xanthan gum concentrations. These results underscore the importance of inulin and xanthan gum in enhancing the cheese’s microbial stability and textural quality. The study concludes that the strategic use of inulin and xanthan gum improves the nutritional profile of buffalo Petit Suisse cheese and optimizes its textural and sensory attributes.

Industrial interest in surfactants of microbial origin has intensified recently due to the characteristics of these compounds, such as biodegradability and reduced toxicity, and their efficiency in removing heavy metals and hydrophobic organic compounds from soils and waters. The aim of this study was to produce a biosurfactant using Candida bombicola URM 3712 in a low-cost medium containing 5.0% molasses, 3.0% corn steep liquor and 2.5% residual frying oil for 144 h at 200 rmp. Measurements of engine oil tension and emulsification were made under extreme conditions of temperature (0 °C, 5 °C, 70 °C, 100 °C and 120 °C), pH (2–12) and NaCl concentrations (2–12), demonstrating the stability of the biosurfactant. The isolated biosurfactant was characterized as an anionic molecule with the ability to reduce the surface tension of water from 72 to 29 mN/m, with a critical micellar concentration of 0.5%. The biosurfactant had no toxic effect on vegetable seeds or on Eisenia fetida as a bioindicator. Applications in the removal of heavy metals from contaminated soils under dynamic conditions demonstrated the potential of the crude and isolated biosurfactant in the removal of Fe, Zn and Pb with percentages between 70 and 88%, with the highest removal of Pb being 48%. The highest percentage of removal was obtained using the cell-free metabolic liquid, which was able to remove 48, 71 and 88% of lead, zinc and iron from the soil, respectively. Tests in packed columns also confirmed the biosurfactant’s ability to remove Fe, Zn and Pb between 40 and 65%. The removal kinetics demonstrated an increasing percentage, reaching removal of 50, 70 and 85% for Pb, Zn and Fe, respectively, reaching a greater removal efficiency at the end of 24 h. The biosurfactant was also able to significantly reduce the electrical conductivity of solutions containing heavy metals. The biosurfactant produced by Candida bombicola has potential as an adjuvant in industrial processes for remediating soils and effluents polluted by inorganic contaminants.

The evolution of technological tools, namely affordable sensors for data collection, and the growing concerns about maintaining roads in adequate conditions have promoted the development of continuous pavement monitoring systems. This paper presents the installation and use of an innovative pavement monitoring system, which was developed to measure the effects of vehicle loads and temperature on the performance of a pavement structure. The sensors used are based on fibre Bragg grating optical technology, collecting data about the strains imposed in the pavement and the temperature at which those measurements are made. The site selection for the system’s installation and the essential installation details to ensure successful data collection are addressed. A calibration procedure was implemented by performing falling weight deflectometer tests and passing preweighed heavy vehicles over the sensors. In addition to validating the system installation, the results obtained in the calibration confirmed the importance of adequately choosing the distance between sensors. Differences of 50 mm in the position of the load may cause differences of about 20% to 25% in the resulting strains. These results confirmed the importance of increasing the sensor concentration in wheel paths. Furthermore, for loads between 25 kN and 65 kN, raising the temperature by 8 °C caused an increase of about 20% in the horizontal tensile strains measured in the pavement. In summary, it was possible to conclude that this innovative system is capable of capturing the effects of temperature and vehicle speed on the response of the pavement, which may be considered an advantage of this type of monitoring system when compared to those that are only used to determine the loads applied to the pavement or to characterise the type of vehicle.

Abstract Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. While remarkable treatment advances have been made recently in the form of modulator drugs directly rescuing CFTR dysfunction, there is still considerable scope for improvement of therapeutic effectiveness. Here, we report the application of a high‐throughput screening variant of the Mammalian Membrane Two‐Hybrid (MaMTH‐HTS) to map the protein–protein interactions of wild‐type (wt) and mutant CFTR (F508del), in an effort to better understand CF cellular effects and identify new drug targets for patient‐specific treatments. Combined with functional validation in multiple disease models, we have uncovered candidate proteins with potential roles in CFTR function/CF pathophysiology, including Fibrinogen Like 2 (FGL2), which we demonstrate in patient‐derived intestinal organoids has a significant effect on CFTR functional expression.

Abstract Background Due to ageing of the population the incidence of multimorbidity and polypharmacy is rising. Polypharmacy is a risk factor for medication-related (re)admission and therefore places a significant burden on the healthcare system. The reported incidence of medication-related (re)admissions varies widely due to the lack of a clear definition. Some medications are known to increase the risk for medication-related admission and are therefore published in the triggerlist of the Dutch guideline for Polypharmacy in older patients. Different interventions to support medication optimization have been studied to reduce medication-related (re)admissions. However, the optimal template of medication optimization is still unknown, which contributes to the large heterogeneity of their effect on hospital readmissions. Therefore, we implemented a clinical decision support system (CDSS) to optimize medication lists and investigate whether continuous use of a CDSS reduces the number of hospital readmissions in older patients, who previously have had an unplanned probably medication-related hospitalization. Methods The CHECkUP study is a multicentre randomized study in older (≥60 years) patients with an unplanned hospitalization, polypharmacy (≥5 medications) and using at least two medications from the triggerlist, from Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. Patients will be randomized. The intervention consists of continuous (weekly) use of a CDSS, which generates a Medication Optimization Profile, which will be sent to the patient’s general practitioner and pharmacist. The control group will receive standard care. The primary outcome is hospital readmission within 1 year after study inclusion. Secondary outcomes are one-year mortality, number of emergency department visits, nursing home admissions, time to hospital readmissions and we will evaluate the quality of life and socio-economic status. Discussion This study is expected to add evidence on the knowledge of medication optimization and whether use of a continuous CDSS ameliorates the risk of adverse outcomes in older patients, already at an increased risk of medication-related (re)admission. To our knowledge, this is the first large study, providing one-year follow-up data and reporting not only on quality of care indicators, but also on quality-of-life. Trial registration The trial was registered in the Netherlands Trial Register on October 14, 2018, identifier: NL7449 (NTR7691). https://www.trialregister.nl/trial/7449 .

Este artigo propõe uma técnica para estimação da matriz de impedância de rede vista por um inversor trifásico conectado à rede elétrica. Ela é baseada na injeção de perturbações binárias pseudo-aleatórias de corrente impostas pelo controle do inversor. As perturbações são injetadas nos referenciais dq sincronizados por uma malha de captura de fase (PLL), referente ao sistema de controle (CPLL). Utilizase outro PLL, exclusivamente para a estimação da matriz de impedância síncrona dq (EPLL). Por meio de análises no domínio da frequência, verifica-se que a estimação da impedância é afetada para frequências na banda passante (BP) do EPLL. Consequentemente, a BP deve ser projetada dentro de uma faixa de frequências menor do que aquelas de interesse para a estimação da matriz de impedância. O presente trabalho também aplica o critério generalizado de Nyquist (CGN) para avaliar a estabilidade do sistema. Conclui-se que a seleção equivocada da banda do EPLL pode levar a avaliações incorretas. Além disso, a banda do CPLL pode ser usada para produzir uma matriz de impedância do inversor que assegure maiores margens de estabilidade ao sistema. As discussões apresentadas neste artigo são apoiadas por simulações no software Simulink e por realizações dos controles em tempo real através de uma plataforma Typhoon.

PV modules generally contain several metals that are considered critical and/or strategic and can be recovered. They also contain harmful and toxic metals that pose a threat to the environment and human health, which makes the significance of recycling even greater. This study used mechanically processed waste Si–C (polycrystalline silicon) photovoltaic (PV) panels to obtain highly concentrated recycled metals of interest. The PV panels were comminuted and granulometrically separated before the concentration of the metals of interest could be studied in an electrostatic separator. Some parameters of the electrostatic separator were evaluated, such as the applied voltage, rotation speed of the roll, as well as distance and angle of the electrodes for better separation of the metals of interest (copper, silver, aluminum, and silicon). The results were evaluated by X-ray fluorescence analysis and the proportions of each element in the samples were compared. The results obtained showed that in the comminution and particle size separation process, the greatest mass of material (49.22%) is concentrated in the smallest particle size category, which is smaller than 0.5 mm. This particle size also has higher concentrations of silicon, silver, and aluminum. The best results with the electrostatic separator were obtained using an electric potential difference of 38 kV and a rotation speed of 75 rpm (rotation per minute), where it was possible to concentrate silicon, silver, and aluminum.

Provision of shade reduces radiant heat load on feedlot cattle, thus reducing demand of water and energy for thermoregulation. While the positive effects of shade on animal welfare are widely known, the literature lacks data on the magnitude of its economic impacts. In this study, we propose the concept of novel shade design to prove that a correctly oriented and dimensioned roof structure, which optimizes shade to be displaced within the pens, motivates cattle to seek shade, protect them from short-wave solar radiation, and is resilient to counteract weather adverse conditions. The beneficial outcome is improvement in animal welfare and productive performance, as well as increments on financial return and sustainability. To attest these benefits, eight hundred B. indicus × Bos taurus bulls were randomly assigned in pens with or without shade from a galvanized steel-roof structure. Performance data (e.g., dry matter intake, body weight gain, feed efficiency and hot carcass weight) and heat stress indicators (e.g., subcutaneous temperature, body-surface temperature, respiratory rate and water intake) were assessed along the study period. The economic outcomes derived from shade implementation were determined using the net present value. Meteorological variables were also monitored every 1 min, and grouped in a thermal comfort index for feedlot cattle, the InComfort Index (InCI). The shade structure efficiently reduced radiant heat load on cattle in pens with shade. According to the classification of the InCI, during very hot days (InCI > 0.6; around noon with mean solar radiation above 800 W m−2 and mean air temperature above 33°C), greater proportion (80%) of animals in shaded pens were using shade. Under such circumstances, cattle in shade had water intake reduced by 3.4 L per animal, body temperature was lower by 5°C, subcutaneous temperature was lower by 1°C and respiration rate was lower by 10 breaths min−1 compared to animals in pens without shade (P = 0.0001). Although dry matter intake was similar (P = 0.6805), cattle in pens with shade had higher average daily gain reflected in a heavier hot carcass weight (8 kg animal−1; P = 0.0002). Considering an initial investment of $90 per animal to build a structure that lasts 15 years, the expected payback time is four finishing cycles (~110 days per cycle). In conclusion, this study confirms that the proposed novel shade design is economically profitable, improves performance, and enhances animal welfare.

Abstract Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and its incidence is increasing. Preoperative diagnosis is warranted in order to avoid ‘two‐stage’ procedures that are associated with additional costs and higher radioactive iodine remnant uptake. In the setting of thyroid cancer, somatic BRAF V600E‐mutations are highly specific for PTC and can be analyzed in aspirates from fine‐needle aspiration cytology (FNAC). The ‘gold standard’ to perform FNAC is ultrasound guidance. Here, we analyze whether adding BRAF V600E‐mutation analysis could be of value in palpation‐guided FNACs. A total of 430 consecutive patients were included. Ultrasound‐guided FNACs were performed in 251 patients and 179 patients underwent palpation‐guided FNACs. BRAF V600E‐mutation analysis was performed using two methods, an allele‐specific polymerase chain reaction (PCR) analyzed by capillary gel electrophoresis (PCR/Qiaxcel), and a droplet digital PCR (ddPCR) assay. A total of 80 patients underwent surgery, and histology revealed 25 patients to have PTC. Of the 25 PTCs, 23 (92%) showed a BRAF V600E‐mutation. Both mutation analysis methods (PCR/Qiaxcel and ddPCR) produced concordant results. In the ultrasound‐guided group, the preoperative diagnostic sensitivity of FNAC using the Bethesda classification alone was very high and additional BRAF V600E‐mutation analysis added little to the preoperative diagnostic sensitivity. By contrast, in the palpation‐guided group, by adding BRAF V600E‐mutation analysis, eight instead of four patients were diagnosed of having PTC. This increase in the diagnostic sensitivity was statistically significant (p

Abstract The in vivo correct QT (QTc) assay is used by the pharmaceutical industry to characterize the potential for delayed ventricular repolarization and is a core safety assay mentioned in International Conference on Harmonization (ICH) S7B guideline. The typical telemetry study involves a dose‐response analysis of QTc intervals over time using a crossover (CO) design. This method has proven utility but does not include direct integration of pharmacokinetic (PK) data. An alternative approach has been validated and is used routinely in the clinical setting that pairs pharmacodynamic (PD) responses with PK exposure (e.g., concentration‐QTc (C‐QTc) analysis. The goal of our paper was to compare the QTc sensitivity of two experimental approaches in the conscious dog and non‐human primate (NHP) QTc assays. For timepoint analysis, a conventional design using eight animals (8 × 4 CO) to detect moxifloxacin‐induced QTc prolongation was compared to a PK/PD design in a subset (N = 4) of the same animals. The findings demonstrate that both approaches are equally sensitive in detecting threshold QTc prolongation on the order of 10 ms. Both QTc models demonstrated linearity in the QTc prolongation response to moxifloxacin dose escalation (6 to 46 ms). Further, comparison with human QTc findings with moxifloxacin showed agreement and consistent translation across the three species: C‐QTc slope values were 0.7‐ (dog) and 1.2‐ (NHP) fold of the composite human value. In conclusion, our data show that dog and NHP QTc telemetry with an integrated PK arm (C‐QTc) has the potential to supplement clinical evaluation and improve integrated QTc risk assessment.